A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.
A publication issued at stated, more or less regular, intervals.
"The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.
The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).
7,12-Dimethylbenzanthracene. Polycyclic aromatic hydrocarbon found in tobacco smoke that is a potent carcinogen.
Publications in any medium issued in successive parts bearing numerical or chronological designations and intended to be continued indefinitely. (ALA Glossary of Library and Information Science, 1983, p203)
A group of ALKALOIDS, characterized by a nitrogen-containing necine, occurring mainly in plants of the BORAGINACEAE; COMPOSITAE; and LEGUMINOSAE plant families. They can be activated in the liver by hydrolysis of the ester and desaturation of the necine base to reactive electrophilic pyrrolic CYTOTOXINS.
A benign epithelial tumor of the LIVER.
Perennial herb Symphytum officinale, in the family Boraginaceae, used topically for wound healing. It contains ALLANTOIN, carotene, essential oils (OILS, VOLATILE); GLYCOSIDES; mucilage, resin, SAPONINS; TANNINS; triterpenoids, VITAMIN B12, and ZINC. Comfrey also contains PYRROLIZIDINE ALKALOIDS and is hepatotoxic if ingested.
A species of toxic plants of the Compositae. The poisonous compounds are alkaloids which cause cattle diseases, neoplasms, and liver damage and are used to produce cancers in experimental animals.
Tests to experimentally measure the tumor-producing/cancer cell-producing potency of an agent by administering the agent (e.g., benzanthracenes) and observing the quantity of tumors or the cell transformation developed over a given period of time. The carcinogenicity value is usually measured as milligrams of agent administered per tumor developed. Though this test differs from the DNA-repair and bacterial microsome MUTAGENICITY TESTS, researchers often attempt to correlate the finding of carcinogenicity values and mutagenicity values.
Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.
Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests.
DNA-dependent DNA polymerases found in bacteria, animal and plant cells. During the replication process, these enzymes catalyze the addition of deoxyribonucleotide residues to the end of a DNA strand in the presence of DNA as template-primer. They also possess exonuclease activity and therefore function in DNA repair.
An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
The process by which a DNA molecule is duplicated.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.
A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.
The portion of an interactive computer program that issues messages to and receives commands from a user.
That portion of the electromagnetic spectrum in the visible, ultraviolet, and infrared range.
An effective trypanocidal agent.
Communication between animals involving the giving off by one individual of some chemical or physical signal, that, on being received by another, influences its behavior.
The process by which ELECTRONS are transported from a reduced substrate to molecular OXYGEN. (From Bennington, Saunders Dictionary and Encyclopedia of Laboratory Medicine and Technology, 1984, p270)
Electric conductors through which electric currents enter or leave a medium, whether it be an electrolytic solution, solid, molten mass, gas, or vacuum.
Pheromones that elicit sexual attraction or mating behavior usually in members of the opposite sex in the same species.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.

Induction of AT-specific DNA-interstrand crosslinks by bizelesin in genomic and simian virus 40 DNA. (1/2171)

Bizelesin is a bifunctional AT-specific DNA alkylating drug. Our study characterized the ability of bizelesin to induce interstrand crosslinks, a potential lethal lesion. In genomic DNA of BSC-1 cells, bizelesin formed from approx. 0.3 to 6.03+/-0.85 interstrand crosslinks per 106 base pairs, at 5-100 nM drug concentration, respectively, comparable to the number of total adducts previously determined in the same system (J.M. Woynarowski, M.M. McHugh, L.S. Gawron, T.A. Beerman, Biochemistry 34 (1995) 13042-13050). Bizelesin did not induce DNA-protein crosslinks or strand breaks. A model defined target, intracellular simian virus 40 (SV40) DNA, was employed to map at the nucleotide level sites of bizelesin adducts, including potential interstrand crosslinks. Preferential adduct formation was observed at AT tracts which are abundant in the SV40 matrix associated region and the origin of replication. Many sites, including each occurrence of 5'-T(A/T)4A-3', co-mapped on both DNA strands suggesting interstrand crosslinks, although monoadducts were also formed. Bizelesin adducts in naked SV40 DNA were found at similar sites. The localization of bizelesin-induced crosslinks in AT-rich tracts of replication-related regions is consistent with the potent anti-replicative properties of bizelesin. Given the apparent lack of other types of lesions in genomic DNA, interstrand crosslinks localized in AT-rich tracts, and to some extent perhaps also monoadducts, are likely to be lethal effects of bizelesin.  (+info)

The effect of cotinine or cigarette smoke co-administration on the formation of O6-methylguanine adducts in the lung and liver of A/J mice treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (2/2171)

4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific nitrosamine, induces lung adenomas in A/J mice, following a single intraperitoneal (i.p.) injection. However, inhalation of tobacco smoke has not induced or promoted tumors in these mice. NNK-induced lung tumorigenesis is thought to involve O6-methylguanine (O6MeG) formation, leading to GC-->AT transitional mispairing and an activation of the K-ras proto-oncogene in the A/J mouse. NNK can be metabolized by several different cytochromes P450, resulting in a number of metabolites. Formation of the promutagenic DNA adduct O6MeG is believed to require metabolic activation of NNK by cytochrome P450-mediated alpha-hydroxylation of the methylene group adjacent to the N-nitroso nitrogen to yield the unstable intermediate, methanediazohydroxide. Nicotine, cotinine (the major metabolite of nicotine), and aqueous cigarette tar extract (ACTE) have all been shown to effectively inhibit metabolic activation of NNK to its mutagenic form, most likely due to competitive inhibition of the cytochrome P450 enzymes involved in alpha-hydroxylation of NNK. The objective of the current study was to monitor the effects of cotinine and cigarette smoke (CS) on the formation of O6MeG in target tissues of mice during the acute phase of NNK treatment. To test the effect of cotinine, mature female A/J mice received a single intraperitoneal injection of NNK (0, 2.5, 5, 7.5, or 10 mumole/mouse) with cotinine administered at a total dose of 50 mumole/mouse in 3 separate i.p. injections, administered 30 min before, immediately after, and 30 min after NNK treatment. To test the effect of whole smoke exposure on NNK-related O6MeG formation, mice were exposed to smoke generated from Kentucky 1R4F reference cigarettes at 0, 0.4, 0.6, or 0.8 mg wet total particulate matter/liter (WTPM/L) for 2 h, with a single i.p. injection of NNK (0, 3.75, or 7.5 mumole/mouse) midway through the exposure. Cigarette smoke alone failed to yield detectable levels of O6MeG. The number of O6MeG adducts following i.p. injection of NNK was significantly (p < 0.05) reduced in both lung and liver by cotinine and by cigarette smoke exposure. Our results demonstrate that NNK-induced O6MeG DNA adducts in A/J mice are significantly reduced when NNK is administered together with either cotinine, the major metabolite of nicotine, or the parental complex mixture, cigarette smoke.  (+info)

Effect of cellular ATP depletion on topoisomerase II poisons. Abrogation Of cleavable-complex formation by etoposide but not by amsacrine. (3/2171)

Topoisomerase (topo) II poisons have been categorized into ATP-independent and -dependent drugs based on in vitro studies. We investigated drug-induced topoII-DNA complexes in intact cells almost completely depleted of ATP. Virtually no DNA single-strand breaks (SSBs), as measured by alkaline elution, were detected in energy-depleted cells treated with the topoII poisons etoposide, teniposide, daunorubicin, doxorubicin, mitoxantrone, or clerocidin. This inhibition was reversible; subsequent incubation with glucose restored the level of DNA SSBs. The effect of ATP depletion was specific for topoII, because topoI-mediated cleavable complexes induced by camptothecin were unaffected by ATP depletion. Furthermore, etoposide-induced DNA-protein complexes and DNA double-strand breaks, as measured by filter elution techniques, and topoIIalpha and -beta trapping, as measured by a band depletion assay, were completely inhibited by energy depletion. Differences in drug transport could not explain the effect of ATP depletion. The topoII poison amsacrine (m-AMSA) was unique with respect to ATP dependence. In ATP-depleted cells, m-AMSA-induced DNA SSBs, DNA double-strand breaks, DNA-protein complexes, topoIIalpha and -beta trapping were only modestly reduced. The accumulation of m-AMSA was reduced in ATP-depleted cells, which indicates that drug transport could contribute to the modest decrease in m-AMSA-induced cleavable complexes. In conclusion, drug-induced topoII-DNA complexes were completely antagonized in ATP-depleted cells, except in the case of m-AMSA. One possible interpretation is that m-AMSA mainly produces prestrand passage DNA lesions, whereas the other topoII poisons tested exclusively stabilize poststrand passage DNA lesions in intact cells.  (+info)

A novel trinuclear platinum complex overcomes cisplatin resistance in an osteosarcoma cell system. (4/2171)

Multinuclear platinum compounds have been designed to circumvent the cellular resistance to conventional platinum-based drugs. In an attempt to examine the cellular basis of the preclinical antitumor efficacy of a novel multinuclear platinum compound (BBR 3464) in the treatment of cisplatin-resistant tumors, we have performed a comparative study of cisplatin and BBR 3464 in a human osteosarcoma cell line (U2-OS) and in an in vitro selected cisplatin-resistant subline (U2-OS/Pt). A marked increase of cytotoxic potency of BBR 3464 in comparison with cisplatin in U2-OS cells and a complete lack of cross-resistance in U2-OS/Pt cells were found. A detailed analysis of the cisplatin-resistant phenotype indicated that it was associated with reduced cisplatin accumulation, reduced interstrand cross-link (ICL) formation and DNA platination, microsatellite instability, and reduced expression of the DNA mismatch repair protein PMS2. Despite BBR 3464 charge and molecular size, in U2-OS and U2-OS/Pt cells, BBR 3464 accumulation and DNA-bound platinum were much higher than those observed for cisplatin. In contrast, the frequency of ICLs after exposure to BBR 3464 was very low. The time course of ICL formation after drug removal revealed a low persistence of these types of DNA lesions induced by BBR 3464, in contrast to an increase of DNA lesions induced by cisplatin, suggesting that components of the DNA repair pathway handle the two types of DNA lesions differently. The cellular response of HCT116 mismatch repair-deficient cells was consistent with a lack of influence of mismatch repair status on BBR 3464 cytotoxicity. Because BBR 3464 produces high levels of lesions different from ICLs, likely including intra-strand cross-links and monoadducts, the ability of the triplatinum complex to overcome cisplatin resistance appears to be related to a different mechanism of DNA interaction (formation of different types of drug-induced DNA lesions) as compared with conventional mononuclear complexes rather than the ability to overcome specific cellular alterations.  (+info)

Biomarkers for exposure to ambient air pollution--comparison of carcinogen-DNA adduct levels with other exposure markers and markers for oxidative stress. (5/2171)

Human exposure to genotoxic compounds present in ambient air has been studied using selected biomarkers in nonsmoking Danish bus drivers and postal workers. A large interindividual variation in biomarker levels was observed. Significantly higher levels of bulky carcinogen-DNA adducts (75.42 adducts/10(8) nucleotides) and of 2-amino-apidic semialdehyde (AAS) in plasma proteins (56.7 pmol/mg protein) were observed in bus drivers working in the central part of Copenhagen, Denmark. In contrast, significantly higher levels of AAS in hemoglobin (55.8 pmol/mg protein), malondialdehyde in plasma (0. 96 nmol/ml plasma), and polycyclic aromatic hydrocarbon (PAH)-albumin adduct (3.38 fmol/ microg albumin) were observed in the suburban group. The biomarker levels in postal workers were similar to the levels in suburban bus drivers. In the combined group of bus drivers and postal workers, negative correlations were observed between bulky carcinogen-DNA adduct and PAH-albumin levels (p = 0.005), and between DNA adduct and [gamma]-glutamyl semialdehyde (GGS) in hemoglobin (p = 0.11). Highly significant correlations were found between PAH-albumin adducts and AAS in plasma (p = 0.001) and GGS in hemoglobin (p = 0.001). Significant correlations were also observed between urinary 8-oxo-7, 8-dihydro-2'-deoxyguanosine and AAS in plasma (p = 0.001) and PAH-albumin adducts (p = 0.002). The influence of the glutatione S-transferase (GST) M1 deletion on the correlation between the biomarkers was studied in the combined group. A significant negative correlation was only observed between bulky carcinogen-DNA adducts and PAH-albumin adducts (p = 0.02) and between DNA adduct and urinary mutagenic activity (p = 0.02) in the GSTM1 null group, but not in the workers who were homozygotes or heterozygotes for GSTM1. Our results indicate that some of the selected biomarkers can be used to distinguish between high and low exposure to environmental genotoxins.  (+info)

Detection of benzo[a]pyrene diol epoxide-DNA adducts in embryos from smoking couples: evidence for transmission by spermatozoa. (6/2171)

Tobacco smoking is deleterious to reproduction. Benzo[a]pyrene (B[a]P) is a potent carcinogen in cigarette smoke. Its reactive metabolite induces DNA-adducts, which can cause mutations. We investigated whether B[a]P diol epoxide (BPDE) DNA adducts are detectable in preimplantation embryos in relation to parental smoking. A total of 17 couples were classified by their smoking habits: (i) both partners smoke; (ii) wife non-smoker, husband smokes; and (iii) both partners were non-smokers. Their 27 embryos were exposed to an anti-BPDE monoclonal antibody that recognizes BPDE-DNA adducts. Immunostaining was assessed in each embryo and an intensity score was calculated for embryos in each smoking group. The proportion of blastomeres which stained was higher for embryos of smokers than for non-smokers (0.723 versus 0.310). The mean intensity score was also higher for embryos of smokers (1.40+/-0.28) than for non-smokers (0.38+/-0.14; P = 0.015), but was similar for both types of smoking couples. The mean intensity score was positively correlated with the number of cigarettes smoked by fathers (P = 0.02). Increased mean immunostaining in embryos from smokers, relative to non-smokers, indicates a relationship with parental smoking. The similar levels of immunostaining in embryos from both types of smoking couples suggest that transmission of modified DNA is mainly through spermatozoa. We confirmed paternal transmission of modified DNA by detection of DNA adducts in spermatozoa of a smoker father and his embryo.  (+info)

In vitro reactions of butadiene monoxide with single- and double-stranded DNA: characterization and quantitation of several purine and pyrimidine adducts. (7/2171)

We have previously shown that butadiene monoxide (BM), the primary metabolite of 1,3-butadiene, reacted with nucleosides to form alkylation products that exhibited different rates of formation and different stabilities under in vitro physiological conditions. In the present study, BM was reacted with single-stranded (ss) and double-stranded (ds) calf thymus DNA and the alkylation products were characterized after enzymatic hydrolysis of the DNA. The primary products were regioisomeric N-7-guanine adducts. N-3-(2-hydroxy-3-buten-1-yl)adenine and N-3-(1-hydroxy-3-buten-2-yl)adenine, which were depurinated from the DNA more rapidly than the N-7-guanine adducts, were also formed. In addition, N6-(2-hydroxy-3-buten-1-yl)deoxyadenosine and N6-(1-hydroxy-3-buten-2-yl)deoxyadenosine were detected and evidence was obtained that these adducts were formed by Dimroth rearrangement of the corresponding N-1-deoxyadenosine adducts, not while in the DNA, but following the release of the N-1-alkylated nucleosides by enzymatic hydrolysis. N-3-(2-hydroxy-3-buten-1-yl)deoxyuridine adducts, which were apparently formed subsequent to deamination reactions of the corresponding deoxycytidine adducts, were also detected and were stable in the DNA. Adduct formation was linearly dependent upon BM concentration (10-1000 mM), with adduct ratios being similar at the various BM concentrations. At a high BM concentration (750 mM), the adducts were formed in a linear fashion for up to 8 h in both ssDNA and dsDNA. However, the rates of formation of the N-3-deoxyuridine and N6-deoxyadenosine adducts increased 10- to 20-fold in ssDNA versus dsDNA, whereas the N-7-guanine adducts increased only slightly, presumably due to differences in hydrogen bonding in ssDNA versus dsDNA. These results may contribute to a better understanding of the molecular mechanisms of mutagenesis and carcinogenesis of both BM and its parent compound, 1,3-butadiene.  (+info)

Idoxifene derivatives are less reactive to DNA than tamoxifen derivatives, both chemically and in human and rat liver cells. (8/2171)

The drug tamoxifen shows evidence of genotoxicity, and induces liver tumours in rats. Covalent DNA adducts have been detected in the liver of rats treated with tamoxifen, and these arise through metabolism at the alpha-position to give an ester which reacts with DNA. (E)-1-(4-iodophenyl)-2-phenyl-1-[4-(2-pyrrolidinoethoxy)phenyl]-but-1-en e (idoxifene) is an analogue of tamoxifen in which formation of DNA adducts is greatly reduced; we could not detect any adducts in the DNA of cultured rat hepatocytes treated with 10 microM idoxifene, after analysis by the 32P-post-labelling method. The metabolite (Z)-4-(4-iodophenyl)-4-[4-(2-pyrrolidinoethoxy)phenyl]-3-phenyl-3-but en-2-ol (alpha-hydroxyidoxifene) gave adducts in rat hepatocytes, but far fewer than the corresponding tamoxifen metabolite. In human hepatocytes, neither idoxifene nor tamoxifen induced detectable levels of DNA adducts. We prepared the alpha-acetoxy ester of idoxifene as a model for the ultimate reactive metabolite formed in rat liver. It was less reactive than alpha-acetoxytamoxifen, as might be expected on mechanistic grounds. It reacted with DNA in the same way, to give adducts which were probably N2-alkyldeoxyguanosines, but to a lower extent. All these results indicate that idoxifene is much less genotoxic than tamoxifen, and should therefore be a safer drug.  (+info)

TY - JOUR. T1 - Smoking-related dna adducts. T2 - P-postlabeling analysis of 7-methylguanine in human bronchial and lymphocyte dna. AU - Mustonen, Rütta. AU - Schoket, Bernadette. AU - Hemminki, Kari. PY - 1993/1/1. Y1 - 1993/1/1. N2 - 7-methylguanine DNA adducts were determined in macroscopically normal bronchial specimens and peripheral blood lymphocytes of 20 patients undergoing pulmonary surgery. A recently developed 32P-postlabeling assay was applied with anion exchange chromatography as an adduct enrichment method. The material consisted of 13 smokers and 7 non-smokers. The mean bronchial 7-methylguanine levels of 11 smokers and 6 non-smokers were 17.3 and 4.7 adducts/107 nucleotides. In lymphocyte DNA, the respective mean levels were 11.5 and 2.3 adducts/107 nucleotides. The bronchial DNA adduct levels in smokers were statistically higher than those in non-smokers. Among 5 smokers, for whom both bronchial and lymphocyte DNA was available, 7-methylguanine levels correlated in the two ...
Bulky DNA adducts are considered a potential biomarker of cancer risk. In this study, the association between various lifestyle, environmental, and genetic factors and the levels of bulky DNA adducts in peripheral leukocytes was examined in a study group nested within a population-based prospective Danish cohort. At enrollment, blood samples were collected and information on lifestyle, including dietary and smoking habits, obtained. Previously, bulky DNA adducts were measured in 245 individuals who developed lung cancer and 255 control members of the cohort. Of these 500 individuals, data on 375 individuals were included in this study, excluding 125 cases, which developed lung cancer within the first 3 yr after blood sampling. Bulky DNA adduct levels were measured by 32P-postlabeling technique and polymorphisms in carcinogen metabolism and DNA repair genes were determined. Potential predictors of bulky DNA adduct levels were analyzed by univariate and multivariate regression analyses. Women ...
Background: Bulky DNA adducts are markers of exposure to genotoxic aromatic compounds, which reflect the ability of an individual to metabolically activate carcinogens and to repair DNA damage. Polycyclic aromatic hydrocarbons (PAHs) represent a major class of carcinogens that are capable of forming such adducts. Factors that have been reported to be related to DNA adduct levels include smoking, diet, body mass index (BMI), genetic polymorphisms, the season of collection of biologic material, and air pollutants.. Methods: We pooled 11 studies (3,600 subjects) in which bulky DNA adducts were measured in human white blood cells with similar 32P-postlabeling techniques and for which a similar set of variables was available, including individual data on age, gender, ethnicity, batch, smoking habits, BMI, and season of blood collection, and a limited set of gene variants.. Results: Lowest DNA adduct levels (P = 0.006) were observed in the spring (median = 0.50 adducts per 108 nucleotides), followed ...
Full text for this publication is not currently held within this repository. Alternative links are provided below where available. ...
Disclosed herein are protecting groups for exocyclic amino groups of the base cytosine for use in the synthesis of oligonucleotides and oligonucleoside phosphorothioates, the protecting groups being represented by the formula: --CO--(CH2)0-9 --CH3. In a particularly preferred embodiment, the base cytosine is protected with acetyl (--CO--CH3), and the oligonucleotide or oligonucleoside phosphorothioate incorporating the protected cytosine is subjected to a cleavage/deprotection reagent comprising methylamine and ammonia.
DNA exhibit a number of reactive sites towards electrophilic agents. Addition reactions can thus take on the various heteroatoms of the bases (N7 atoms of purines, exocyclic amino groups, O4 position of T, etc…), on C8 of purines and even on phosphates. A wide range of molecules have been ... More » ...
TY - JOUR. T1 - Determination of carcinogen-DNA adducts by immunoassay. AU - Poirier, M. C.. AU - Liou, S. H.. AU - Reed, E.. AU - Strickland, P. T.. AU - Tockman, M. S.. PY - 1989/1/1. Y1 - 1989/1/1. UR - http://www.scopus.com/inward/record.url?scp=0024522984&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0024522984&partnerID=8YFLogxK. M3 - Review article. C2 - 2664949. AN - SCOPUS:0024522984. VL - 11. SP - 353. EP - 367. JO - Journal of UOEH. JF - Journal of UOEH. SN - 0387-821X. IS - SUPPL.. ER - ...
From her very first lesson, Lena knew she would eventually become certified to teach this wonderful Technique. Over the years, AT has helped her improve her acting, movement and vocal abilities. Auditioning and performing has become a source of pleasure as opposed to a worry or fear. Creating in a room of her peers, which was once daunting and deadening, is now exciting and enlivening.. In addition to acting, Lena has experienced improvement in all areas of her life, including running, meditating, carrying heavy objects, etc…and has helped numerous people with their issues. Whether it be stage fright or back pain that is bothering you, Lena is eager to share what she has learned with the Technique to help solve your problems.. Lena is currently in her final term at the Alexander Education Center of Berkeley under Giora Pinkas, John Baron, and Robert Britton. Before she began her training in Berkeley, Lena studied the Alexander Technique for a total of 8 years under various teachers including ...
2-Hexenal is an α,β-unsaturated carbonyl compound which is mutagenic, genotoxic and forms cyclic 1,N2-propanodeoxyguanosine adducts like similar propenals for which carcinogenicity was shown, e.g. acrolein or crotonaldehyde. Since humans have a permanent intake of 2-hexenal via vegetarian food this genotoxic compound is considered to play a role in human carcinogenicity. The data base is, however, presently not sufficient for a cancer risk assessment. To date no long term carcinogenicity study on 2-hexenal has been published. Detection of respective DNA adducts of this substance in animals or humans could allow cancer risk assessment. Therefore, we have developed a 32P-post-labeling technique based on nuclease P1 enrichment and TLC separation of the labeled adducts. The respective adducts are stable over a wide pH range from pH 4 to pH 11 and relatively stable against nuclease P1. The detection limit was 0.03 adducts per 106 nucleotides and the recovery was 10%. With this method we have shown ...
Our previous studies suggested that body fluids such as serum can serve as a novel surrogate for DNA-containing tissues to overcome the major limiting factor of tissue availability in human biomonitoring assessments. We have now examined the detectability of DNA-reactive metabolites (DRMs) in the serum and tissues of male C57BL/6 mice administered up to 10 i.p. injections on alternate days of individual polynuclear aromatic hydrocarbons (PAHs) or a mixture containing 0.01, 0.1, 1.0 and 5.0 mg/kg body wt each of benzo[a]pyrene (BP), cyclopenta[cd]pyrene (CPP) and benzo[k]fluoranthene (BF) in 200μl sunflower oil. Four hours after the last dose, blood serum was separated and incubated with salmon testes DNA (st-DNA).32P-Post-labeling of the st-DNA showed essentially the same adduct pattern as found in the tissue DNA, indicating that DRMs of the PAHs used were presumably sequestered and accumulated in the serum proteins. Serum DRMs were detectable at all doses tested following exposure to a mixture ...
C043931000 - Benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA - Searchable synonyms, formulas, resource links, and other chemical information.
The chemistry of acrolein and crotonaldehyde-derived propano-deoxyguanosine (γ-OH-PdG and α-CH3-γ-OH-PdG) adducts was monitored in the 5´-CpG-3´ sequence within a dodecamer duplex by NMR spectroscopy, in situ, using a series of site-specific 13C- and 15N-edited experiments. One striking phenomenon was the formation of an interstrand DNA cross-link, predominantly a carbinolamine. The cross-link existed in equilibrium with the non-crosslinked aldehyde and its geminal diol hydrate. The ratio of aldehyde/diol increased at higher temperatures. The effects of the pH and complementary bases were examined. Molecular modeling suggested that the carbinolamine linkage should be capable of maintaining Watson-Crick hydrogen bonds at both of the tandem C•G base pairs. In contrast, dehydration of the carbinolamine cross-link to an imine (Schiff base) cross-link, or cyclization of the latter to form a pyrimidopurinone cross-link, was predicted to require disruption of Watson-Crick hydrogen bonds at one ...
High mobility group box (HMGB) proteins are DNA-binding proteins that regulate many important DNA-related processes. They are known to recognize the major lesion present in cisplatin-modified DNA, and have been assumed to ...
The E.Z.N.A.® SQ Tissue DNA Kit provides a reliable method for the isolation of high molecular weight genomic DNA from various types of fresh or frozen tissue samples. This solution based system can process single or multiple samples simultaneously in less than 90 minutes. Samples are lysed with WTL Buffer/Protease and cellular proteins are removed by precipitation. High molecular genomic DNA remains in solution and is purified by isopropanol precipitation. DNA purified using the E.Z.N.A.® SQ Tissue DNA Kit is free of contaminants and enzyme inhibitors making it suitable for downstream applications such as PCR, Southern blotting and restriction enzyme digestion.. ...
A high-titer antiserum has been elicited against TAM-DNA modified to 2.4% with α-acetoxytamoxifen. The TAM-dG adduct formed by this modification is the predominant DNA adduct found in livers of rats exposed to this drug. The antiserum has been used to develop two immunoassays, DELFIA and CIA, with a detection limit for the CIA at 2.6 adducts per 109 nucleotides. By competitive DELFIA, the antiserum has been demonstrated to be specific for TAM in DNA, with cross-reactivities for the individual adduct, the drug or its metabolites, and unmodified DNA occurring only at ∼1000-fold higher concentrations or not at all. The immunogen adduct, TAM-dG, was the first TAM-DNA adduct characterized in livers of TAM-exposed rats (16) . Recently, another major TAM-DNA adduct, the product of a N-desmethylated TAM metabolite, has been demonstrated in rat liver (34, 35, 36, 37) . Preliminary results3 indicate that TAM-DNA antiserum may recognize DNA modified with N-desmethyl-TAM-dG similarly to the immunogen ...
In an article in the April 2000 issue of Cancer Epidemiology, Biomarkers & Prevention, an authors surname, Besaratinia, appeared as Nia. For consistency in the literature, the author would like to revise the author list for that article. The corrected citation appears below.. Besaratinia A, Maas LM, Van Breda SG, Curfs DM, Kleinjans JC, Wouters EF, Van Schooten FJ. Applicability of induced sputum for molecular dosimetry of exposure to inhalatory carcinogens: 32P-postlabeling of lipophilic DNA adducts in smokers and nonsmokers. Cancer Epidemiol Biomarkers Prev 2000;9:367-72.. ...
5202 Pancreatic cancer represents a leading cause of cancer-related mortality, with only limited (,5 years) survival rate. Cigarette smoking has been implicated in the development of pancreatic cancer. Because of the high mortality rate, it is necessary that early biomarkers be developed before the onset of pathological changes. In this study, we analyzed highly lipophilic adducts in the pancreas DNA of non-smokers (n=7.) and smokers (n=8). Tissues were obtained from the U.S. Cooperative Tissue Network, and the isolated DNAs were analyzed by nuclease P1-mediated 32P-postlabeling/TLC. When chromatographed in standard high-salt, high-urea solvents, adducts migrated in the form of diagonal radioactive zones in both non-smokers and smokers; however, the adduct load was significantly (p=0.031) higher in smokers (231±38 adducts/109 nucleotides, mean±SE) compared with non-smokers (94±42 adducts/109 nucleotides). To determine the chemical nature of the adducts, selected smoker DNA samples were ...
exocyclic definition: exterior to a chemical band construction: an exocyclic double-bond.; (of a cyclic chemical) maybe not developing part of, or not connected to the ring; Pertaining to the Exocyclica;…
Couldnt detect gpg so will proceed without verification! , gpg.exe is in C:\texlive\2016\tlpkg\installer\gpg, but is not in the Should be fixed after today, hopefully ;-) Sorry. Norbert ------------------------------------------------------------------------ PREINING, Norbert http://www.preining.info JAIST, Japan TeX Live & Debian Developer GPG: 0x860CDC13 fp: F7D8 A928 26E3 16A1 9FA0 ACF0 6CAC A448 860C DC13 ...
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Multiple exocyclic DNA adducts arise from reactions of lipid and DNA peroxidation products with DNA bases. These endogenous lesions are mutagenic; therefore, monitoring adduct levels may provide a means of assessing genomic exposure to oxidative damage in human populations. The metabolic processing of endogenously formed exocyclic DNA adducts has now been investigated for the purpose of developing non-invasive markers of oxidative damage. The pyrimidopurinone deoxynucleoside adduct, M1dG, was found to undergo enzymatic oxidation to produce 6-oxo-M1dG. The corresponding base adduct, M1G, was subject to sequential oxidation producing first 6-oxo-M1G and then 2,6-dioxo-M1G. The enzymes xanthine oxidoreductase (XOR) and aldehyde oxidase (AO) catalyzed the oxidation of M1dG and M1G. Additionally, the unsubstitued etheno base adduct, 1,N2-etheno-Gua, and the substituted etheno base adduct, heptanone-1,N2-etheno-Gua, were oxidized to produce 2-oxo-etheno-Gua and 2-oxo-hepatanone-etheno-Gua, ...
Resveratrol inhibits benzo[a]pyrene-DNA adduct formation in human bronchial epithelial cells Resveratrol (trans-3,4,5-trihydroxystilbene), a phytoalexin present in various plants and foods, has in several in vitro and in vivo studies demonstrated cancer chemopreventive and chemotherapeutic potential. We investigated the in vitro effect of resveratrol on benzo[a]pyrene (B[a]P) -induced DNA adducts in human bronchial epithelial cells. This was compared to the effect of resveratrol on the expression of the cytochrome P450 (CYP) genes CYP1A1 and CYP1B1 and the formation of B[a]P metabolites. Exposure of BEAS-2B and BEP2D cells to B[a]P and increasing concentrations of resveratrol resulted in a dose- and time-dependent inhibition of DNA adduct formation quantified by (32)P-postlabelling. Supporting this result, resveratrol was shown to inhibit CYP1A1 and CYP1B1 gene expression, as measured by real-time reverse transcriptase-polymerase chain reaction. Also, a significant correlation was found between ...
The depurinating adduct 4-OHE1(E2)-1(α, β)-N7Gua was formed in vitro and in vivo by reaction of E1(E2)-3,4-Q with DNA and after activation of 4-OHE by cytochrome P450 and peroxidases (Tables 3 and 4). CE-Q derived from 4-OHE and 2-OHE react differently with nucleosides and DNA because of their distinctive chemical properties (17). CE-2,3-Q bind to the exocyclic amino groups of dA and dG to form adducts that retain the deoxyribose moiety whereas CE-3,4-Q bind exclusively to the N-7 of Gua, resulting in destabilization of the glycosidic bond and subsequent depurination. CE-2,3-Q form 10-50 times higher levels of stable DNA adducts than CE-3,4-Q (16). CE-3,4-Q, however, give two to three orders of magnitude higher levels of depurinating than stable adducts (Table 3). Thus, CE-2,3-Q produce stable DNA adducts (16), and the corresponding CE do not induce kidney tumors in Syrian golden hamsters (18, 19) whereas CE-3,4-Q form predominantly 4-OHE1(E2)-1(α, β)-N7Gua, and E1-3,4-Q is carcinogenic in ...
Dr. Shun Matsuda reported his research on the visualization of DNA damage-response signals in cultured cells. This technology can be applied to simple and quick detection of genotoxicity. For example, DNA double-strand breaks orderly recruit several proteins and their modifications, such as phosphorylated histone H2AX, MDC1, and ATM, which coordinate DNA damage-response signals. He explained the absolute quantification of the components using mass spectrometry and how it could help to elucidate the stoichiometry and molecular mechanisms of DNA damage response.. Dr. Yoshinori Okamoto reported his research on the development of non-genotoxic tamoxifen analogs. Tamoxifen is a breast cancer drug, but one of its side effects is endometrial cancer. Based on the mechanisms of carcinogenicity with estrogenic activity and DNA adduct formations of the metabolite, new tamoxifen analogs were designed. These analogs exhibited higher anti-breast cancer potential and no DNA-adduct formation activity in animal ...
EZ Blood/Cell DNA Isolation Kit-EZ Blood/Cell DNA Isolation Kit is designed for isolating genomic DNA from whole blood or cells. The kit is based on s
Formation of stable adducts and absence of depurinating DNA adducts in cells and DNA treated with the potent carcinogen dibenzo [a, l] pyrene or its diol epoxides
Ethenobases are promutagenic DNA adducts formed by some environmental carcinogens and products of endogenous lipid peroxidation. Mutation spectra in tumors induced in mice by urethane or its metabolite vinyl carbamate (Vcar) are compatible with 1,N(6)-ethenoadenine (epsilonA) being an initiating lesion in the development of these tumors. As alkylpurine-DNA-N-glycosylase (APNG) releases epsilonA from DNA in vitro, wild-type and APNG-/- C57Bl/6J mice were treated with Vcar and levels of epsilonA and 3,N(4)-ethenocytosine (epsilonC), which is not a substrate of APNG, were analyzed in liver and lung DNA. At 6 h after the last dose, levels of epsilonA were 1.6-fold higher in DNA from APNG-/- mice and subsequently persisted at higher levels for longer than in DNA from wild-type animals, confirming that epsilonA is released by APNG in vivo. In contrast, approximately 14-fold lower levels of epsilonC were induced by Vcar, and the kinetics of formation and persistence of epsilonC was similar in the two ...
Ixr1 is a yeast HMG-domain protein that binds specifically to DNA adducts formed by the antitumor drug cisplatin. Interruption of the IXR1 gene in yeast desensitizes cells to cisplatin. This effect is unrelated to a natural function of Ixr1, which is to repress the transcription of COX5b. Ixr1 inter …
An extensive literature survey on correlation of biomarkers resulted in the following preliminary conclusions: • No significant correlation between individual pairs of DNA adducts was found in a number of the 32P-postlabelling and immunoassay studies, indicating limited overlapping of the substrate specificity of the different DNA adduct methods. • Attempts to show correlations between a group of related DNA adduct structures and a chemically specific single DNA adduct structure by using the same type of methodology gave controversial results. These suggest the co-existence of both closely linked and independent metabolic activation pathways for complex mixtures of xenobiotics, and may also reflect differences in the kinetics of DNA adduct formation and elimination. • A larger number of studies revealed a positive correlation between DNA adduct levels in target and surrogate tissues than did not find a correlation. Correlation may depend on exposure dose and the metabolic capacity of the ...
Sikdar S, Joehanes R, Joubert BR, Xu C, Vives-Usano M, Rezwan F, Felix J, Ward JM, Guan W, Richmond RC, Brody JA, Kupers LK, Baiz N, Haberg SE, Smith JA, Reese SE, Aslibekyan S, Hoyo C, Dhingra R, Markunas CA, Xu T, Reynolds LM, Just AC, Mandaviya PR, Ghantous A, Bennett BD, Wang T, BIOS-Consortium, Bakulski KM, Melen E, Zhao S, Juin J, Herceg Z, van Meurs JB, Taylor JA, Baccarelli A, Murphy SK, Liu Y, Minthe-Kaas MC, Deary IJ, Nystad W, Waldenberger M, Annesi-Maesano I, Conneely K, Jaddoe VW, Arnett D, Snieder H, Kardia SL, Relton CL, Ong KK, Ewart S, Moreno-Macias H, Romieu I, Sotoodehnia N, Fornage M, Motsinger-Reif A, Koppelman GH, Bustamante M, Levy D, London SJ. 2019. Comparison of smoking-related DNA methylation between newborns from prenatal exposure and adults from personal smoking. Epigenomics 11(13):1487-1500. doi:10.2217/epi-2019-0066 PMID:31536415 PMCID:PMC6836223 ...
1K29: The exocyclic 1,N2-deoxyguanosine pyrimidopurinone M1G is a chemically stable DNA adduct when placed opposite a two-base deletion in the (CpG)3 frameshift hotspot of the Salmonella typhimurium hisD3052 gene.
The Genomic DNA Maxi Kit (Blood/Cultured Cell) is optimized for DNA purification (including genomic, mitochondrial and viral DNA) from up to 10 ml of frozen blood or fresh blood and up to 1 x 108 cultured cells using an efficient maxiprep system. This DNA Extraction Kit uses Protease to reduce hemoglobin contamination while chaotropi
The difference in size between 160 million bp and 3 billion bp is not that great relative to total cell size and both UV and X-rays do get to the DNA and damage it, despite the many obstacles, and if the DNA was only composed of genes then the damage would always be potentially serious. UV does damage DNA as do external carcinogens from tobacco smoke, food, pollution etc, and the most common cause of DNA adduction is endogenous oxidative damage - these are all mainly repaired by excision mechanisms which dont involve strand breaks. X-rays cause breaks which can be lethal - and it is good that they are lethal, much better to sacrifice a single cell via apoptosis than allow it to divide with a damaged genome. But if there are strand breaks in gene(s) important for apoptosis, the chances of which would be much higher in the smaller functional only genome, then the chances of allowing the creation of transformed cells would be much greater too. With a larger genome the chances of any X-ray damage ...
The difference in size between 160 million bp and 3 billion bp is not that great relative to total cell size and both UV and X-rays do get to the DNA and damage it, despite the many obstacles, and if the DNA was only composed of genes then the damage would always be potentially serious. UV does damage DNA as do external carcinogens from tobacco smoke, food, pollution etc, and the most common cause of DNA adduction is endogenous oxidative damage - these are all mainly repaired by excision mechanisms which dont involve strand breaks. X-rays cause breaks which can be lethal - and it is good that they are lethal, much better to sacrifice a single cell via apoptosis than allow it to divide with a damaged genome. But if there are strand breaks in gene(s) important for apoptosis, the chances of which would be much higher in the smaller functional only genome, then the chances of allowing the creation of transformed cells would be much greater too. With a larger genome the chances of any X-ray damage ...
マウス・モノクローナル抗体 ab57070 交差種: Hu 適用: WB,IHC-P,ICC/IF,sELISA…DNA Polymerase Kappa/POLK抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの Antibody…
No all any recurrent mutations are cancer hotspots, say researchers who have demonstrated that putting recurrent mutations into genomic context can distinguish between passengers and drivers of cancer
SEATTLE, Oct. 21, 2013 /PRNewswire/ -- Cell Therapeutics Announces Results from Preclinical Study of Pixantrone (PIXUVRI®) Presented at the AACR-NCI-EORTC...
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Im having some strange results with GPG. Im getting quite a few BAD signatures from people whos public keys are on my keyring and even the occasional bad signature from MYSELF. I know that there are some options that are on (or off) by default in GPG due to OpenPGP standards, but that conflict with PGP default settings. However, I dont think Ive ever seen an actual PGP signature on this list (most are GPG). Any suggestions? -Alex ...
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This is the first attempt for the direct detection of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human placental DNA samples by solid-matrix phosphorescence (SMP). Six samples were investigated, and SMP emission spectra and the corresponding second derivative SMP spectra were obtained for all the samples. Numerous excitation and emission wavelengths were studied for detecting PAH-DNA add
The sensitivity of various methods suitable for biomonitoring the exposure to genotoxicants was compared in an animal model. The results were related to the presence of genotoxic effects in the target organ. Groups of male Wistar rats were given one oral dose of 0, 0.1, 1, 10 or 200 mg 2-acetylaminofluorene (2-AAF)/5 ml dimethyl sulphoxide/kg body weight. Peripheral blood cells, excreta, liver and spleen were collected at different time intervals after dosing. Mutagenicity in urine and extracts of faeces was determined using the Ames test with Salmonella typhimurium TA98 with and without S9 and with and without ??-glucuronidase. Genotoxic effects were studied by measuring DNA-adduct formation in lymphocytes, liver and spleen, and sister-chromatid exchanges (SCEs) in lymphocytes. DNA adducts were measured with immunochemical techniques and postlabelling methods. Mutagenecity in urine and faeces, collected during the first 24 h after treatment, was detected at 2-AAF doses of 1 mg/kg b.w. and ...
Electrophilic arylnitrenium ions are considered to be the ultimate reactive intermediates formed by metabolism of mutagenic and carcinogenic arylamines and nitroarenes; they can produce DNA damage by reaction with specific sites on DNA bases. We studied their formation, reactivity and the genotoxic sequelae of their reactions with cellular DNA to understand the mutagenic and carcinogenic activities of arylamines and nitroarenes as a function of their chemical structure. Arylnitrenium ions were generated by the convenient non-metabolic procedure, photolysis of arylazides, to study the reactivity of these ultimate intermediates with DNA, by means of 32P-postlabelling, and the induction of histidine reversions in Salmonella, HPRT mutations and sister chromatid exchange in mammalian (Chinese hamster V79) cells. Good correlations were observed between the DNA-binding potencies and the mutagenic and SCE-inducing potencies of the arylnitrenium ions, among these the nitrenium ions derived from the heterocyclic
What is the acronym meaning of CRC Crit Rev Toxicol, what does the acronym CRC Crit Rev Toxicol stand for, CRC Crit Rev Toxicol abbreviation means
It is evident from many different experiments, that the human nucleotide excision repair (NER) apparatus first distinguishes structural DNA perturbations caused...
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1LAS: Structure of an oligodeoxynucleotide containing a 1,N(2)-propanodeoxyguanosine adduct positioned in a palindrome derived from the Salmonella typhimurium hisD3052 gene: Hoogsteen pairing at pH 5.2.
V. J. Melendez-Colon, Smith, C. Allen, Seidel, A., Luch, A., Platt, K. L., and Baird, W. M., Formation of stable adducts and absence of depurinating DNA adducts in cells and DNA treated with the potent carcinogen dibenzo [a, l] pyrene or its diol epoxides, Proceedings of the National Academy of Sciences, vol. 94, pp. 13542-13547, 1997. ...
Tissue DNA Extraction and Tissue RNA Isolation - Some animal and human tissues are the toughest samples to isolate high-quality DNA or RNA
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Dr. Reece and Professor Hulse conducted an evidence-informed narrative review of research exploring the hypothesis that cannabis use causes errors in human DNA.. This research shouldnt be viewed on par with a systemic review, but there are no signs that the two researchers have cherry-picked the evidence. That is why I strongly believe in their research, even tho there are better ways of conducting research.. What these two men have done raises some questions, and those questions will lead to further research. ...
The overall objective of this proposal is to understand how dietary energy balance and especially obesity influences genome stability at endogenous mutational ...
Sulc M, Mrizova I, Cerna T, Frei E, Eckschlager T, Adam V, Kopeckova K, Stiborova M. Effectiveness of human cytochrome P450 3A4 present in liposomal and microsomal nanoparticles in formation of covalent DNA adducts by ellipticine. Neuro Endocrinol Lett. 2016 Dec; 37(Suppl 1): 95-102 ...
.. ۞ ۞ Intermediates at the [email protected] immunoglobulin heavy locus the experimental evidence for the association 3-PRIME @REPAIR EXONUCLEASE 1; TREX1 in the ATRIP-RPA-ssDNA complex.}] remove mismatched, modified, fragmented, and normal nucleotides using a panel of seven VH FR1 family-specific primers incorporated in a single reaction using variable region-(VH) and joining (JH) region-specific primers corresponding…
The Index page for the reference article: Katselou M, Papoutsis I, Nikolaou P, Spiliopoulou C, Athanaselis S Old opioids, new concerns: the case of acetylfentanyl Forensic Toxicol 2016
This modification is available as part of a custom oligonucleotide configuration. Please use OLIGObuilder™ to generate pricing and order or contact us to speak with a customer service representative. ...
DNA adducts are a type of DNA damage. DNA damage is considered to be the primary cause of carcinogenesis. Adduct Adductomics ... "DMBA-DNA adduct" in a scientific journal refers to a piece of DNA that has DMBA attached to it. The presence of such an adduct ... of a specific type of DNA adduct called M1dG. When a chemical binds to DNA, the DNA becomes damaged, and proper and complete ... a naturally occurring product of lipid peroxidation DNA adducts include: etheno-DNA adducts: 1,N(6)-etheno-2-deoxyadenosine ( ...
... curing operation were compared with the peripheral blood lymphocyte concentrations of two nitrosamine-related DNA adducts. N7- ... methylguanine (N7mdG) and 06-methylguanine (O6mdG), and with the activity of the enzyme that repairs 06mdG adducts, 06- ... alkylguanine-DNA alkyltransferase (AGT). The occupational personal breathing zone (PB ... The 06mdG adduct concentrations were much lower than those of N7mdG, ranging from non-detectable to 12.7 06mdG adducts/lO ...
Camptothecin-stabilized topoisomerase I-DNA adducts cause premature termination of transcription.. Bendixen C1, Thomsen B, ... the data suggest that part of the cytotoxicity of camptothecin is mediated through adduct formation on transcribed DNA, ... The antitumor agent camptothecin stabilizes type I topoisomerase-DNA complexes. One of the primary cellular responses to ... be attributed to physical blockage of the RNA polymerase by camptothecin-stabilized topoisomerase I-DNA complexes on the DNA ...
... but form the same types of adducts at the same sites on DNA. However, the DNA adducts are differentially recognized by a number ... The cytotoxicity of platinum compounds is thought to be determined primarily by their DNA adducts. Cisplatin and oxaliplatin ... but form the same types of adducts at the same sites on DNA. However, the DNA adducts are differentially recognized by a number ... Recognition and processing of cisplatin- and oxaliplatin-DNA adducts Crit Rev Oncol Hematol. 2005 Jan;53(1):3-11. doi: 10.1016/ ...
New Method Pairs Artificial Nucleotide, Mutant Polymerase to Detect DNA Adducts. Jan 21, 2015 ... Home » New Method Pairs Artificial Nucleotide, Mutant Polymerase to Detect DNA Adducts ... Alkylating substances such as tobacco smoke and environmental toxins can create mutagenic alkylguanine DNA adducts. This type ... DNA Quantification and Normalization with Promega QuantiFluor Dyes on the Fluent Laboratory Automation Solution ...
This aflatoxin-DNA adduct excretion product serves as a biomarker of the biologically effective dose of aflatoxin, and elevated ... Loeb has predicted that a 2-fold reduction in mutation rates, as might be anticipated from this decline in DNA adduct burden, ... Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer. Patricia A. Egner, Jin- ... 1, this aflatoxin-DNA adduct excretion product serves as a biomarker of the biologically effective dose of aflatoxin and ...
The findings of recent studies which assessed macromolecular adducts formed by carcinogens were used to illustrate the ... DNA adducts and related biomarkers in assessing the risk of complex mixtures.. ... NIOSH-Author; Biological-monitoring; Bioassays; Carcinogenesis; Risk-analysis; Laboratory-animals; DNA-adducts; Molecular- ... The findings of recent studies which assessed macromolecular adducts formed by carcinogens were used to illustrate the ...
Popp W., Schell C., Kraus R., Vahrenholz C., Wolf R., Radtke J., Bierwirth K., Norpoth K. DNA strand breakage and DNA adducts ... PAH-DNA adduct levels explained tumor outcome. For example, Nesnow et al. (10) found a correlation between the formation of DNA ... Bulky DNA adducts were measured by 32P-postlabelling (in the majority of studies) or ELISA. Six studies measured adducts in ... DNA adducts, according to smoking status. An overall 83% excess of adduct levels was found in cases compared with controls in ...
... breast and cervix has been analysed for DNA adducts using the nuclease P1 modification of the 32P post-labelling technique. ... Purified DNA from human lung, liver, bladder, pancreas, ... DNA adducts in different tissues of smokers and non-smokers Int ... Purified DNA from human lung, liver, bladder, pancreas, breast and cervix has been analysed for DNA adducts using the nuclease ... Smokers and former smokers tended to have higher adduct levels than non-smokers in the tissues examined but this was only ...
... no depurination DNA adducts of DMBA were detected. The amount of stable DNA adducts observed with denatured DNA was 70% lower ... The stable DNA adducts were analyzed by the 32P-postlabeling method. Almost 4 times as much of the depurination adduct 7-MBA-12 ... Identification and quantitation of 7,12-dimethylbenz[a]anthracene-DNA adducts formed in mouse skin.. Devanesan PD1, RamaKrishna ... In this paper we report the identification and quantitation of the depurination and stable DMBA-DNA adducts formed in mouse ...
In Aim 3 we will investigate DNA complexed with histone proteins in nucleosomes, the fundamental packaging unit of DNA in cells ... However, why certain DNA lesions are NER-resistant and others are not when NER is normal, is not understood. The objective of ... However, not all DNA lesions are equally effective in promoting human diseases: while lesions can be excised by the human ... The novel insights into the DNA lesion recognition mechanisms of NER that we will gain may lead to the development of more ...
... derived DNA adducts. In this study we report the formation of these DHP-derived DNA adducts in blood DNA of rats fed ... leucocyte DNA can bind with DHP to form a set of DHP-derived DNA adducts generated in liver; (ii) DHP-derived DNA adducts in ... the levels of DHP-derived DNA adduct in blood and liver were determined by 32P-postlabeling/HPLC. Maximum DNA adduct formation ... The levels of the DHP-derived DNA adducts in blood of rats receiving 0.1 and 1.0 mg/kg doses were 12.9 and 51.8 adducts/107 ...
Such combinations of chemicals with DNA are called DNA adducts. Because adducts interfere with normal DNA replication, their ... between the location of DNA adducts and mutation, the investigators compared the regions in DNA where adducts formed to those ... analyzed the chemical structure of the adducts, and (3) determined in which region of the DNA the adducts formed. When the ... Relationship of Nitropyrene-Derived DNA Adducts to Carcinogenesis. EPA Grant Number: R828112C055. Subproject: this is ...
... dna · animal cell · article · colony formation · dna adduct · dna content · dna damage · dna synthesis · drug dna binding · ... unscheduled dna synthesis · Animal · Benzo(a)pyrene · beta Carotene · Carotenoids · DNA Adducts · DNA Damage · DNA Repair · ... P-DNA adduct levels by enhancing DNA-repair activities. Because the formation of B[a]P-DNA adducts is considered to be an early ... DNA adduct levels were significantly lower in WBC as compared with lung. Nonetheless, overall B[a]P-DNA adduct levels in WBC ...
Covalent protein-DNA adducts or tightly bound proteins represent a major challenge to the DNA replication machinery. DNA ... proposed to be dependent on formation of the MTase-DNA adducts ( 24). Finally, aza-C-dependent MTase-DNA adducts have been ... 5-Azacytidine-Induced Methyltransferase-DNA Adducts Block DNA Replication In vivo. H. Kenny Kuo, Jack D. Griffith and Kenneth N ... 5-Azacytidine-Induced Methyltransferase-DNA Adducts Block DNA Replication In vivo. H. Kenny Kuo, Jack D. Griffith and Kenneth N ...
DNA adducts and DNA damage. DNA methyltransferase 1 (DNMT1) expression was significantly higher in smokers than non-smokers ... Tobacco-specific carcinogens induce hypermethylation, DNA adducts and DNA damage in Bladder Cancer. September 13, 2017 Smoking ... DNA adducts, and extensive DNA damage in BLCA cells. Co-treatment of BLCA cells with these carcinogens and the methylation ... DNA adducts, DNA damage. These findings were confirmed through the isotopic labeled metabolic flux analysis. Screens using ...
... in DNA was investigated in male rats and mice exposed by ... of using adducts in hemoglobin as a surrogate for DNA adducts ... have been used to support the concept of using adducts in hemoglobin as a surrogate for DNA adducts in target tissues. The ... Hemoglobin adducts were lost at a greater rate than predicted by normal erythrocyte life span. The loss of 7-HEG from DNA was ... Molecular dosimetry of DNA and hemoglobin adducts in mice and rats exposed to ethylene oxide. ...
Etheno-DNA adducts are generated from the metabolism of exogenous carcinogens and endogenous lipid peroxidation. We and others ... Etheno-DNA adducts are generated from the metabolism of exogenous carcinogens and endogenous lipid peroxidation. We and others ... Ultrasensitive UPLC-MS-MS Method for the Quantitation of Etheno-DNA Adducts in Human Urine. Shiwei Cui 1,2,3. ... "Ultrasensitive UPLC-MS-MS Method for the Quantitation of Etheno-DNA Adducts in Human Urine." Int. J. Environ. Res. Public ...
... which increases the stability of Top2-DNA adducts (Pommier et al., 2010). These unprocessed Top2-DNA adducts block DNA ... To quantify Top2-DNA adducts in Xenopus genomic DNA in the presence and absence of DNA repair factors, we adapted a protocol ... Top2-DNA adducts are thought to be excised throughout the cell cycle. Indeed, we observe resection defects from Top2-DNA adduct ... To ascertain the requirements for CtIP and MRN in replication of DNA bearing Top2-DNA adducts, we examined DNA replication in ...
Leukocyte DNA adducts were analysed blindly using the 32P DNA postlabelling technique. The intensity of adduct patterns was ... Objectives were to investigate prospectively the ability of DNA adducts to predict cancer, and to study the determinants of DNA ... Bulky DNA adducts and lung cancer risk: a prospective study in EPIC investigation. Marco Peluso, Armelle Munnia, Domenico Palli ... Our large prospective study suggests that the presence of bulky 32P-postlabelling DNA adducts in the WBC of non-smokers may ...
... Lenka ... 10-epoxide-DNA Adducts in People Dermally Exposed to PAHs," Journal of Immunology Research, vol. 2014, Article ID 834389, 6 ...
"DNA Adducts" by people in this website by year, and whether "DNA Adducts" was a major or minor topic of these publications. ... "DNA Adducts" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject ... A 32P-postlabeling method for the detection of adducts in the DNA of human fibroblasts exposed to sulfur mustard. Chem Biol ... Relationship between polycyclic aromatic hydrocarbon-DNA adducts, environmental tobacco smoke, and child development in the ...
BaP-DNA adduct formation in vivo. The BaP-DNA adduct pattern obtained from in vivo treatments consisted of one major adduct ... BaP-DNA adduct formation in the livers of HRN mice was ~ sevenfold higher than in WT mice. BaP-DNA adduct formation in HBRN ... DNA adduct levels were calculated as described (Phillips and Arlt 2014). Results were expressed as DNA adducts/108 nucleotides. ... adduct 2 was the predominant DNA adduct formed with the formation of dG-N 2 -BPDE (adduct 1) being much lower (Supplementary ...
The DNA Damage Response Kinases DNA-dependent Protein Kinase (DNA-PK) and Ataxia Telangiectasia Mutated (ATM) Are Stimulated by ... The most frequent DNA adduct made by the anticancer drug cisplatin, the 1,2-intrastrand d(GpG) cross-link, as well as the minor ... HMG-domain proteins specifically inhibit the repair of the major DNA adduct of the anticancer drug cisplatin by human excision ... HMG-domain proteins specifically inhibit the repair of the major DNA adduct of the anticancer drug cisplatin by human excision ...
DNA polymerase η (Pol-η) is a crucial polymerase that allows cancer cells to cope with the cisplatin-DNA adducts that are ... DNA polymerase η (Pol-η) is a crucial polymerase that allows cancer cells to cope with the cisplatin-DNA adducts that are ... Crystal structure of human DNA polymerase eta in ternary complex with a cisplatin DNA adduct. *DOI: 10.2210/pdb4EEY/pdb ... DNA polymerase eta. A. 435. Homo sapiens. Mutation(s): 1 Gene Names: POLH, RAD30, RAD30A, XPV. EC: 2.7.7.7. ...
... in complex with a DNA substrate containing a bulky DNA lesion and incoming nucleotides. The DNA lesion is derived from an ... In the present study, the major BP diol epoxide adduct in DNA, BP-N(2)-deoxyguanosine (BP-dG), was placed at a template-primer ... Bypass of Major Benzopyrene-dG Adduct by Y-Family DNA Polymerase with Unique Structural Gap. *DOI: 10.2210/pdb2IA6/pdb ... A structural gap in Dpo4 supports mutagenic bypass of a major benzo[a]pyrene dG adduct in DNA through template misalignment.. ...
Reactive metabolites may form specific DNA adducts and induce the tumors observed in mice. ... Reactive metabolites may form specific DNA adducts and induce the tumors observed in mice. To determine DNA adducts in specific ... HPEG was the major adduct and was about three times higher in Type II cells than in total lung. For mice, DNA adduct levels in ... Quantification of DNA adducts formed in liver, lungs, and isolated lung cells of rats and mice exposed to 14C-styrene by nose- ...
APE1, the DNA base excision repair protein, regulates the removal of platinum adducts in sensory neuronal cultures by NER.. [ ... Overexpressing DNA repair activity mutant APE1 (226 + 177APE1), with only redox activity was ineffective suggesting it is the ... proposed mechanism for this neurotoxicity is the formation of platinum adducts in sensory neurons that could contribute to DNA ... Overexpressing a mutant APE1 (C65 APE1), which only has DNA repair activity, but not its other significant redox-signaling ...
DNA adducts formed by 2-amino-3,8-dimethyl imidazole 〔4, 5-f〕 quinoxaline in rat liver: dose-response on chronic administration ... Nuclease P1-mediated enhancement of sensitivity of ^,32,P-postlabeling test for structually diverse DNA adducts REDDY M. V. ... Decreased Levels of 2-Amino-3-methylimidazo[4,5-f]quinoline-DNA Adducts in Rats Treated with β-Carotene, α-Tocopherol and ... Enhanced sensitivity of ^,32,P-post-labeling analysis of aromatic carcinogen : DNA adducts GUPTA R. C. ...
  • citation needed] Under experimental conditions for study, such DNA adducts are induced by known carcinogens, of which commonly used is DMBA (7,12-dimethylbenz(a)anthracene). (wikipedia.org)
  • The findings of recent studies which assessed macromolecular adducts formed by carcinogens were used to illustrate the potential and current limitations of this approach. (cdc.gov)
  • Bulky" DNA adducts represent an integrated marker of exposure to aromatic compounds, and of the ability of the individual to metabolically activate carcinogens and to repair DNA damage. (aacrjournals.org)
  • Tobacco-specific carcinogens induce hypermethylation, DNA adducts and DNA damage in Bladder Cancer. (urotoday.com)
  • In vitro exposure to the tobacco smoke carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (BaP) led to increase in levels of methylated metabolites, DNA adducts, and extensive DNA damage in BLCA cells. (urotoday.com)
  • Co-treatment of BLCA cells with these carcinogens and the methylation inhibitor 5-aza-2'-deoxycytidine (AZA) rewired the methylated metabolites, DNA adducts, DNA damage. (urotoday.com)
  • Etheno-DNA adducts are generated from the metabolism of exogenous carcinogens and endogenous lipid peroxidation. (mdpi.com)
  • Background: Bulky DNA adducts are markers of exposure to genotoxic aromatic compounds, which reflect the ability of an individual to metabolically activate carcinogens and to repair DNA damage. (ccceh.org)
  • Polycyclic aromatic hydrocarbons (PAHs) represent a major class of carcinogens that are capable of forming such adducts. (ccceh.org)
  • Many chemical carcinogens and their in vivo activated metabolites react readily with genomic DNA, and form covalently bound carcinogen-DNA adducts. (uncg.edu)
  • There were both a higher frequency of G: C↑T: A mutations and a higher average hydrophobic DNA adduct level in females than in male patients, even though the level of exposure to carcinogens from cigarette smoking was lower among the females than among the males. (oup.com)
  • It readily forms DNA adducts, generating potential carcinogens such as glyoxalated deoxycytidine (gdC). (salford.ac.uk)
  • A variety of DNA adducts derived from various classes of carcinogens, including aromatic amines, polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines, alkylating agents, aldehydes, volatile carcinogens, as well as oxidative damage have been reported. (umn.edu)
  • The primary effect of aza-C is the prohibition of cytosine methylation, which results in covalent methyltransferase-DNA (MTase-DNA) adducts at cytosine methylation sites. (aacrjournals.org)
  • Numerous chemicals as well as radiation can lead to covalent protein-DNA adducts, but little is known about the consequences of these adducts in vivo . (aacrjournals.org)
  • the covalent protein-DNA linkage is then reversed and the enzyme dissociates from the DNA ( 5 ). (aacrjournals.org)
  • The consequences of covalent MTase-DNA adduct formation can also be important. (aacrjournals.org)
  • Through a transesterification reaction, the catalytic tyrosine of the enzyme forms a transient phosphotyrosine covalent linkage, generating a nick in the DNA. (rupress.org)
  • The potent carcinogen BP is metabolized to diol epoxides that form covalent adducts with cellular DNA. (rcsb.org)
  • Oxaliplatin functions predominantly via the formation of toxic covalent drug-DNA adducts. (aacrjournals.org)
  • These findings confirm the classification of ALKBH1 as an AP lyase, identify the primary and a secondary lysine residues involved in the lyase reaction, and demonstrate that the protein forms a covalent adduct with the 5′ DNA product. (biochemj.org)
  • Anticancer activity of the antibiotic Mitomycin C (MC) is connected with its covalent binding to DNA. (jbsdonline.com)
  • What could be possible consequences of covalent bond mitochondrial and genomic DNA adduct by Fluoroquinolones, our study was done by Fluoroquinolone Toxicity Study NFP. (stackexchange.com)
  • Psoralen intercalates into DNA and on exposure to ultraviolet (UVA) radiation can form monoadducts and covalent interstrand cross-links (ICL) with thymines, preferentially at 5'-TpA sites in the genome, inducing apoptosis . (wikipedia.org)
  • 14 C] Adriamycin treatment (25 nM) resulted in 4.4 ± 1.0 adducts/ 10 7 bp (∼1300 adducts/cell) in MCF-7 breast cancer cells, representing the best sensitivity and precision reported to date for the covalent binding of Adriamycin to DNA. (elsevier.com)
  • Many compounds can react with DNA forming covalent modifications, so-called DNA adducts, which can influence crucial biological processes. (openrepository.com)
  • The latter reacts with cellular DNA to form covalent adducts that can, if not removed by cellular DNA repair mechanisms, cause mutations and the initiation of tumorigenesis in animal model systems, and probably in humans. (elsevier.com)
  • Covalent adducts of the carcinogenic polycyclic aromatic hydrocarbon (+)-anti-benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide ((+)-anti-BPDE) in polynucleotides have been studied by fluorescence spectroscopy. (chalmers.se)
  • MeIQx is converted within cells to a reactive derivative which forms a major covalent adduct at carbon-8 of guanine in DNA. (nyu.edu)
  • (9) have shown that the main metabolite of benzo( a )pyrene forms adducts in the same codon of the p53 gene where characteristic mutations are found in the lungs of smokers. (aacrjournals.org)
  • Effect of eugenol on the mutagenicity of benzo[a]pyrene and the formation of benzo[a]pyrene-DNA adducts in the X-lacZ-transgenic mouse. (tudelft.nl)
  • The DNA lesion is derived from an environmentally widespread carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene (BP). (rcsb.org)
  • Antibodies generated against benzo(a)pyrene diol epoxide modified DNA were used to investigate adducts in skin biopsies of coal tar treated psoriasis patients. (eurekamag.com)
  • Accommodation of a 1S-(-)-benzo[c]phenanthrenyl-N6-dA adduct in the Y-family Dpo4 DNA polymerase active site: structural insights through molecular dynamics simulations. (sigmaaldrich.com)
  • Molecular modeling and molecular dynamics simulations have been performed to elucidate feasible structures in the Y-family Dpo4 DNA polymerase for the 1S-(-)-trans-anti-B[c]Ph-N6-dA adduct, derived from the fjord region polycyclic aromatic hydrocarbon (PAH) benzo[c]phenanthrene. (sigmaaldrich.com)
  • The MC-mono-dG adducts are repaired by the nucleotide excision repair (NER) mechanism, which is similar to what occurs with other bulky DNA adducts, such as benzo(a)pyrene diol epoxide-dG adducts and cyclobutane pyrimidine dimers (CPD) photoproducts ( 9 , 10 ). (pubmedcentralcanada.ca)
  • We could detect benzo (a) pyrene diol-epoxide-albumin adduct in smoker and cake oven workers. (nii.ac.jp)
  • Several solution fluorescence parameters were acquired for the four tetrol hydrolysis products of benzo[a]pyrene-trans-7,8-dihydrodiol9,10-epoxide (BPDE)-DNA adducts, tetrols complexed with DNA, and BPDE-DNA adducts in several methanol/water solvents. (osapublishing.org)
  • In vitro benzo[a]pyrene diol epoxide (BPDE)-induced DNA adducts in cultured peripheral lymphocytes have been shown to be a phenotypic biomarker of individual's DNA repair phenotype that is associated with cancer risk. (duke.edu)
  • The benzo- b -acronycine derivative S23906-1 alkylates guanine nucleobases in the minor groove of the DNA helix and presents an original ability to locally open the double helix of DNA, which appears to be associated with its cytotoxic activity. (biochemj.org)
  • Normal tissue from 23 of these aforementioned 27 matched tissue sets was analyzed for PAH-DNA adduct levels using antiserum elicited against DNA modified with r,7t8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE). (lancs.ac.uk)
  • Benzo pyrene-induced DNA adducts and gene expression profiles in target and non-target organs for carcinogenesis in mice. (environment-health.ac.uk)
  • Target organs for benzo[a]pyrene (BaP) carcinogenicity in mice (lung, spleen and forestomach) and three non-target organs (liver, colon and glandular stomach) were investigated for DNA adducts by 32P-postlabelling, for gene expression changes by cDNA microarray and for miRNA expression changes by miRNA microarray after exposure of animals to BaP. (environment-health.ac.uk)
  • Human lung cancer exhibits a high frequency of transver-sion mutations at G: C base pairs of the p 53 gene, possibly the result of DNA damage by cigarette smoke constituents, most notably benzo[ a ]pyrene. (oup.com)
  • Ricerca di addotti fra benzo(a)pirene diolepossido e DNA in differenti cellule mediante spettrofotometria a fluorescenza sincrona. (elsevier.com)
  • The levels of benzo(a)pyrene diolepoxide(BPDE)-DNA adducts were measured in rat and human cells by synchronous fluorescence spectrophotometry. (elsevier.com)
  • Both competitive and non-competitive assays using CE/LIF were developed for the determination of DNA adducts of benzo(a)pyrene diol epoxide (BPDE). (geoscience.net)
  • These substrates contain adducts of (6-4) photoproducts, N-acetyl-2-aminofluorene-, 1-amino-pyrene-, BPDE (benzo[a]pyrene diol epoxide)- and fluorescein that are different in many aspects such as molecular structure and size, DNA disruption mode (e.g. base stacking or non-stacking), as well as chemical properties. (elsevier.com)
  • UVR exposure or pretreatment with aTRP or FICZ also sensitized cells to benzo(a)pyrene (B[a]P)-induced DNA adduct formation. (nyu.edu)
  • DNA adducts in scientific experiments are used as biomarkers of exposure and as such are themselves measured to reflect quantitatively, for comparison, the amount of carcinogen exposure to the subject organism, for example rats or other living animals. (wikipedia.org)
  • DNA adducts and related biomarkers in assessing the risk of complex mixtures. (cdc.gov)
  • The authors conclude that these early studies are encouraging in that macromolecular adducts and related biomarkers can ultimately be useful in identifying the operational carcinogenic constituents of complex mixtures and in estimating whether their effect is additive or interreactive. (cdc.gov)
  • ii) DHP-derived DNA adducts in blood can serve as a potential non-invasive biomarkers for assessing the exposure to riddelliine. (mdpi.com)
  • The biomarkers are DNA and protein adducts and cytogenetic effects. (tudelft.nl)
  • Screens using smoke associated metabolites and DNA adducts could provide robust biomarkers and improve individual risk prediction in BLCA smokers. (urotoday.com)
  • We examined analytical methods of albumin adduct and conducted a cross sectional study of polycyclic aromatic hydrocarbon exposure and molecular biomarkers including DNA adducts and albumin adduct in cake oven workers. (nii.ac.jp)
  • The use of exocyclic adducts as biomarkers offers a promising tool in studies of cancer etiology and prevention, particularly for human neoplasias in which the causative factors and mechanisms are still poorly understood. (iarc.fr)
  • The volume includes sections on ultrasensitive detection methods, formation from exogenous and endogenous sources, DNA repair, physical chemical approaches to structural elucidation, use as biomarkers and their role in mutagenesis and carcinogenesis. (iarc.fr)
  • DNA adducts from various DNA-damaging agents can act both as biomarkers and as a measurement of the actual damage of the genome. (openrepository.com)
  • DNA adducts are believed to play a central role in the induction of cancer in cigarette smokers and are proposed as being potential biomarkers of cancer risk. (umn.edu)
  • Taken together, the data suggest that part of the cytotoxicity of camptothecin is mediated through adduct formation on transcribed DNA, resulting in interference with transcriptional elongation. (nih.gov)
  • (10) found a correlation between the formation of DNA adducts by PAHs, and the induction of ras mutations and lung tumor in mice. (aacrjournals.org)
  • We have previously shown that riddelliine, a naturally occurring genotoxic pyrrolizidine alkaloid, induces liver tumors in rats and mice through a genotoxic mechanism mediated by the formation of a set of eight 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5Hpyrrolizine ( DHP)-derived DNA adducts. (mdpi.com)
  • In this study we report the formation of these DHP-derived DNA adducts in blood DNA of rats fed riddelliine. (mdpi.com)
  • In an adduct formation and removal experiment, male and female F344 rats (8 weeks of age) were administered riddelliine by gavage at a single dose of 10.0 mg/kg body weight in 0.1 M phosphate buffer. (mdpi.com)
  • Maximum DNA adduct formation occurred at 48 hr after treatment. (mdpi.com)
  • Eugenol was not mutagenic by itself By 32P-postlabelling analysis of the liver DNA using an analysis method with chromatographic conditions for B[a]P-DNA adducts, no effect of eugenol on the formation of B[a]P-DNA adducts in the λ-lacZ-transgenic mouse was found. (tudelft.nl)
  • Evidence for adduct formation in vivo has been presented ( 9 , 10 ). (aacrjournals.org)
  • Embryonic stem cells and transgenic mice with reduced levels of cytosine MTase were more resistant to aza-dC than the wild-type, suggesting that protein-DNA adduct formation mediates aza-dC cytotoxicity ( 21 ). (aacrjournals.org)
  • Aza-dC treatment also causes induction of p53 DNA damage response, proposed to be dependent on formation of the MTase-DNA adducts ( 24 ). (aacrjournals.org)
  • This reaction also entails formation of a transient protein-DNA adduct, in this case between a tyrosine residue at each active site of the Top2 dimer and the 5′ phosphates of DNA strands on both sides of the DSB. (rupress.org)
  • Mechanism of site-specific psoralen photoadducts formation in triplex DNA directed by psoralen-conjugated oligonucleotides. (umassmed.edu)
  • In vitro incubations carried out with BaP-pretreated microsomal fractions, BaP and DNA resulted in significantly higher BaP-DNA adduct formation with WT microsomal fractions compared to those from HRN or HBRN mice. (springer.com)
  • Adduct formation (i.e. 10-(deoxyguanosin- N 2 -yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydro-BaP [dG- N 2 -BPDE]) correlated with observed CYP1A activity and metabolite formation (i.e. (springer.com)
  • BaP-DNA adduct levels (i.e. dG- N 2 -BPDE) in vivo were significantly higher (~ sevenfold) in liver of HRN mice than WT mice while no significant difference in adduct formation was observed in liver between HBRN and WT mice. (springer.com)
  • Pathways of BaP biotransformation and BaP-DNA adduct formation catalysed by CYP1A1 and mEH. (springer.com)
  • The overall results of this study indicate that DNA adduct formation does not play an important role in styrene tumorigenicity in chronically exposed mice. (rti.org)
  • One proposed mechanism for this neurotoxicity is the formation of platinum adducts in sensory neurons that could contribute to DNA damage. (sigmaaldrich.com)
  • Of particular importance is the finding that tunnel finishing work is associated with an increased level of DNA adducts formation in PBMC. (bmj.com)
  • Oxaliplatin-DNA adduct formation was correlated with oxaliplatin cytotoxicity for each cell line as measured by the MTT viability assay. (aacrjournals.org)
  • The resultant proximate mutagens often need further activation by phase II transferases for formation of reactive species that form adducts with DNA. (ruc.dk)
  • Frandsen, H 1996, Food derived carcinogenic amnoimidazoazaarenes: bioactivation and DNA adduct formation . (ruc.dk)
  • SCE formation after exposure of CHO cells prelabelled with BrdU or biotin-dUTP to various DNA-damaging agents. (ebscohost.com)
  • Formation of sister chromatid exchanges (SCE) is a mechanism of repair or bypass of DNA damage during S phase. (ebscohost.com)
  • Although SCE have been studied for a long time, the types of DNA lesions involved and the role of 5-bromodeoxyuridine (BrdU) in SCE formation are a matter of debate. (ebscohost.com)
  • The biological significance of this exposure is, as yet, unknown but in situ NOC formation is bacterially catalysed suggesting that NOC formation and potentially DNA alkylation will vary throughout the large bowel. (bmj.com)
  • CONCLUSIONS DNA alkylation varied within the large bowel possibly due to in situ NOC formation and was highest in areas of the colon and rectum where the highest incidence of large bowel tumours occurs, suggesting that DNA alkylation may play a role in the aetiology of colorectal cancer. (bmj.com)
  • We tested the hypothesis that BITC inhibits B[a]P tumorigenicity in mouse lung by inhibiting DNA adduct formation, and compared the effects of BITC and PEITC. (eurekamag.com)
  • Effects on 7,8-dihydroxy-9, 10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)-DNA adduct formation were evaluated in DNA from mice treated with isothiocyanates and B[a]P, and killed 2-120h later. (eurekamag.com)
  • However, differences in BPDE-DNA adduct formation do not appear to explain fully the contrasting effects of BITC and PEITC on B[a]P-induced lung tumorigenesis. (eurekamag.com)
  • Previously, we detected the formation of 3-NBA-derived DNA adducts in rodent tissues by 32P-postlabeling, all of which are derived from reductive metabolites of 3-NBA bound to purine bases, but structural identification of these adducts has not yet been reported. (ovid.com)
  • However, the molecular mechanism linking adduct formation to cellular consequences is not precisely known. (biochemj.org)
  • Therefore, factors other than PAH-DNA adducts may be responsible for promotion of tumor formation in the human prostate. (lancs.ac.uk)
  • RESULTS: BaP-DNA adduct formation occurred in all six organs at levels that did not distinguish between target and non-target. (environment-health.ac.uk)
  • Chemoprotection against the formation of colon DNA adducts from the food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the rat. (semanticscholar.org)
  • In addition, ISC-4 effectively inhibited methyl-DNA adduct formation in mice fed diet supplemented with ISC-4 for two weeks and then treated with the tobacco procarcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. (aacrjournals.org)
  • Chemical activation results can be explained by formation of a bisadduct (conditions I) and a monoadduct (conditions II) respectively, both in the N2-position of guanine bases of DNA, in contrast to acid and electrodic activations which give mono and bisadducts respectively with DNA preferentially in the N(7) position of guanines (where the electroactive group is situated). (jbsdonline.com)
  • When DNA is exposed to UVC radiation, adjacent pyrimidines become covalently linked by the formation of a four-membered ring structure that results from saturation of their respective 5,6 double bonds ( 3 ). (iiarjournals.org)
  • Single-stranded DNA also permits the formation of dimers between nonadjacent pyrimidines ( 4 ). (iiarjournals.org)
  • UVA may alter cell membrane components ( 5 ), induce DNA-protein crosslinking ( 6 ), and increase formation of reactive oxygen species (ROS). (iiarjournals.org)
  • These findings point to features of XPC-RAD23B-bulky DNA adduct complexes that may involve the formation of NER-productive or unproductive forms of binding that depend on the structural and stereochemical properties of the DNA adducts studied. (elsevier.com)
  • Investigations in RAW264.7 macrophages indicate the presence of high basal levels of M1dG (1 adduct per 106 nucleotides) and the endogenous formation of 6-oxo-M1dG. (vanderbilt.edu)
  • A major drawback in assessing gdC formation in cellular DNA has been methodologic sensitivity. (salford.ac.uk)
  • In the present study, we investigated the anti-initiating effects of five polymeric black tea polyphenol (PBP) fractions, by determining their effects on the formation of [ 3 H]-B( a )P-derived DNA adducts as well as the activity of cytochrome P-450 isozymes CYP 1A1 and 1A2 in vitro employing rat liver microsomes. (begellhouse.com)
  • PBP 1-3 inhibited both the microsome catalyzed [ 3 H]-B( a )P-derived DNA adduct formation as well as the activity of CYP 1A1 and 1A2 as assessed by the decreased formation of resorufin from the respective substrates. (begellhouse.com)
  • The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin-DNA adduct detection and revealed adduct formation within an hour of drug treatment. (elsevier.com)
  • These results are discussed collectively in terms of the requirement and contribution of structural elements of the anthracyclines for the formation of DNA adducts. (edu.au)
  • In particular, arylamine-DNA adduct formation has been confirmed in various human tissues and is believed to induce mutation. (grantome.com)
  • The present study had the dual objective of evaluating the formation of DNA adducts in the whole thoracic aorta of Sprague-Dawley rats, exposed whole-body to cigarette smoke for 28 consecutive days, and of investigating the effects of chemopreventive agents given orally during the same period. (elsevier.com)
  • We determined whether UVR exposure sensitized human keratinocytes to PAH-induced DNA adduct formation. (nyu.edu)
  • αNF, an AhR antagonist, suppressed UVR-, aTRP-, and FICZ-mediated induction of CYP1A1 and CYP1B1 and inhibited B[a]P-induced DNA adduct formation. (nyu.edu)
  • and blocked the sensitization of HaCaT cells to B[a]P-induced DNA adduct formation. (nyu.edu)
  • Pretreatment with α-naphthoflavone or 17-AAG blocked FICZ-mediated induction of CYP1A1 and CYP1B1, and suppressed the increased B[a]P-induced DNA adduct formation. (nyu.edu)
  • Collectively, these results suggest that sunlight may activate AhR signaling and thereby sensitize cells to PAH-mediated DNA adduct formation. (nyu.edu)
  • In the CYP450-expressing cells, nanomolar doses of AFB 1 -induced DNA adduct formation including AFB 1 -N 7 -guanine, -pyrimidyl and -diol adducts. (elsevier.com)
  • OBJECTIVE: We selected factors known or hypothesized to affect in utero adduct formation and repair and examined their associations with adduct levels in neonates. (ku.dk)
  • We have summarized research conducted since 2012 on DNA adduct formation in smokers. (umn.edu)
  • We also discuss common issues related to measuring DNA adducts in humans, including the development and validation of analytical methods and prevention of artifact formation. (umn.edu)
  • The results show that the most favorable arrangement for excimer formation of the BPDE-dG adducts is in a 5'(dCdG-BPDE).5'(dCdG-BPDE) sequence, where the pyrenyl chromophores interact in the minor groove. (chalmers.se)
  • Without effective DNA repair, which happens naturally under normal circumstances, this can lead to carcinogenesis, the beginnings of cancer. (wikipedia.org)
  • DNA damage is considered to be the primary cause of carcinogenesis. (wikipedia.org)
  • This type of DNA damage is often a first step in carcinogenesis, but information on these rare, site-specific modifications is hard to come by. (genomeweb.com)
  • Because adducts interfere with normal DNA replication, their presence can result in mutations that may ultimately affect a gene's function and initiate carcinogenesis. (epa.gov)
  • This is believed to be an important mechanism of carcinogenesis in both rodents ( 20-22 ) and smokers ( 23, 24 ) because pob-DNA adducts have been detected in animals treated with NNK and in the lung tissue from smokers ( 24 ). (aacrjournals.org)
  • In humans, exposure to sunlight may cause skin cancer and UV-induced DNA adducts, leading to downstream genome instability which can affect skin carcinogenesis. (iiarjournals.org)
  • Role of methyl-DNA adducts in carcinogenesis have been well characterized and the current paradigm is that methyl- DNA adducts are more important than POB-DNA adducts in the etiology of tobacco-induced cancers. (elsevier.com)
  • Mustonen, R , Schoket, B & Hemminki, K 1993, ' Smoking-related dna adducts: P-postlabeling analysis of 7-methylguanine in human bronchial and lymphocyte dna ', Carcinogenesis , vol. 14, no. 1, pp. 151-154. (elsevier.com)
  • The long term goal of our research program is to elucidate the molecular mechanisms of DNA adduct-induced chemical carcinogenesis. (grantome.com)
  • The levels of the DHP-derived DNA adducts in blood of rats receiving 0.1 and 1.0 mg/kg doses were 12.9 and 51.8 adducts/10 7 nucleotides. (mdpi.com)
  • Results: Lowest DNA adduct levels (P = 0.006) were observed in the spring (median = 0.50 adducts per 108 nucleotides), followed by summer (0.64), autumn (0.70), and winter (0.85). (ccceh.org)
  • We have now prepared 3-NBA-derived DNA adduct standards for 32P-postlabeling by reactingN-acetoxy-3-aminobenzanthrone (N-Aco-ABA) with purine nucleotides. (ovid.com)
  • Here, we report that M1dG levels in intact DNA were increased from basal levels of 1 adduct per 108 nucleotides to 2 adducts per 106 nucleotides following adenine propenal treatment of RKO, HEK293 or HepG2 cells. (vanderbilt.edu)
  • We also found that M1dG in genomic DNA was oxidized in a time-dependent fashion to a single product, 6-oxo-M1dG, (to ~ 5 adducts per 107 nucleotides) and that this oxidation correlated with a decline in M1dG levels. (vanderbilt.edu)
  • Accelerator mass spectrometry (AMS) is a highly sensitive technique used for the quantification of adducts following exposure to carbon-14- or tritium-labeled chemicals, with detection limits in the range of one adduct per 10(11)-10(12) nucleotides. (elsevier.com)
  • The mean bronchial 7-methylguanine levels of 11 smokers and 6 non-smokers were 17.3 and 4.7 adducts/10 7 nucleotides. (elsevier.com)
  • In lymphocyte DNA, the respective mean levels were 11.5 and 2.3 adducts/10 7 nucleotides. (elsevier.com)
  • In the in vitro experiment, DNA adduct levels were significantly higher using the salting-out procedure (63.2 +/- 13.7 adducts per 10(8) nucleotides, n = 9) as compared with the phenol-extraction (14.3 +/- 0.8). (maastrichtuniversity.nl)
  • The presence of such an adduct indicates prior exposure to a potential carcinogen, but does not by itself indicate the presence of cancer in the subject animal. (wikipedia.org)
  • O6-methylguanine DNA adducts associated with occupational nitrosamine exposure. (cdc.gov)
  • Analysis of the ordinal exposure categories (high, medium/high, medium/low and no exposure) yielded a statistically significant association with having detectable 06mdG adducts (Kendall's tb = -0.253, asymptotic SE = 0.096). (cdc.gov)
  • Although no association was found between PBZ exposure and either the N7mdG adduct concentrations or AGT activity, the significant positive association between working in and near the VS department and the presence of 06mdG adducts, which have mutagenic potential, provides evidence to link nitrosamine exposure one step closer to human cancer by demonstrating an association between external nitrosamine exposures and cancer-related biological effects. (cdc.gov)
  • The level of bulky adducts in WBCs has been shown to correlate with external exposure to PAHs 3 in a few investigations. (aacrjournals.org)
  • An investigation is presented of occupational exposure to polycyclic aromatic hydrocarbons (PAH) in a carbon-electrode manufacturing plant, as assessed by three monitoring methods, viz, environmental monitoring of the external dose by analysis of personal air samples, biological monitoring of the internal dose by analysis of urinary 1-hydroxypyrene (1-OHpyrene), and biological effect monitoring by dosimetry of PAH-DNA adducts in blood lymphocytes. (tudelft.nl)
  • Clear external and internal exposure was thus demonstrated for workers of the high and intermediate exposure groups, but this did not result in a measurable effect at the DNA level in blood lymphocytes. (tudelft.nl)
  • To determine DNA adducts in specific tissues and cell types, rats and mice were exposed to 160 ppm [ring-U-14C]styrene by nose-only inhalation for 6 h in a recirculating exposure system. (rti.org)
  • At 0 and 42 h after exposure, the two isomeric N7-guanine adducts of SO (measured together, HPEG) were present in liver at 3.0 ± 0.2 and 1.9 ± 0.3 (rat) and 1.2 ± 0.2 and 3.2 ± 0.5 (mouse) per 108 bases. (rti.org)
  • Conclusions: In this large pooled analysis, we have found only weak associations between bulky DNA adducts and exposure variables. (ccceh.org)
  • Adducts with DNA have also been found in animals after exposure to these compounds. (ruc.dk)
  • the DNA adduct rate was not significantly increased in workers, but correlated with exposure to PAHs in a semiquantitative manner. (ebscohost.com)
  • The assay was then utilised to quantitate O6-MedG adducts formed by exposure of DNA with MNU. (le.ac.uk)
  • Dr. Roger W. Giese and colleagues at Northeastern University developed sensitive and specific techniques for measuring polycyclic aromatic hydrocarbon (PAH)-DNA adducts, a class of DNA adducts associated with exposure to constituents of diesel emissions and other combustion products. (healtheffects.org)
  • Good correlation between the adduct and internal exposure dose was observed. (nii.ac.jp)
  • Publications] Zang J.: 'Aromatic DNA adducts in coke over workers in relation to exposure, lifestyle and qematic polymorphism of metabolic enzymes. (nii.ac.jp)
  • BACKGROUND The pro-mutagenic lesion O 6 -methyldeoxyguanosine ( O 6 -MedG), a marker of exposure to many N -nitroso compounds (NOC), can be detected in normal and tumour DNA isolated from colorectal tissue. (bmj.com)
  • 7 We have previously shown, in two separate studies, that the pro-mutagenic lesion O 6 -methyldeoxyguanosine ( O 6 -MedG), a marker of exposure to many NOC, can be detected in normal and tumour DNA isolated from individuals with colorectal cancer. (bmj.com)
  • The presence of DNA adducts in 44% of the subjects and high levels of Hb adducts in these non-smokers indicate environmental sources of exposure to 4-ABP. (oup.com)
  • The detection of BPDE-DNA adducts may be used in biomonitoring and experimental studies for determining of exposure to BP even when applied as a constituent of complex mixtures. (elsevier.com)
  • BPDE is a potent environmental carcinogen, and the ultrasensitive assays for BPDE-DNA adducts are potentially useful for monitoring human exposure to this carcinogen and for studying cellular repair of DNA damage. (geoscience.net)
  • Exposure to fine particulate matter and nitrogen dioxide was associated with significantly higher adducts in the Danish subsample only. (ku.dk)
  • In the case of pol eta, the efficiency and fidelity of translesion synthesis in vitro is very similar to that previously observed with cyclobutane TT dimers, suggesting that pol eta is likely to be involved in error-free bypass of Pt adducts in vivo. (nih.gov)
  • These results imply that aza-C-induced MTase-DNA adducts block DNA replication in vivo . (aacrjournals.org)
  • We hypothesize that oxaliplatin-DNA adduct levels formed in vivo in peripheral blood mononuclear cells (PBMC) are proportional to tumor shrinkage caused by FOLFOX therapy. (aacrjournals.org)
  • Similarly, dG3′p-C8-N-ABA and dA3′p-N6-ABA cochromatographed with two other adducts formed in various organs of rats or mice treated either with 3-NBA or 3-ABA, whereas dG3′p-C8-C2-ABA did not cochromatograph with any of the adducts foundin vivo. (ovid.com)
  • The roles of NER and BER will be evaluated ex vivo using cells with deficient repair proteins using a HPLC- MS/MS assay to measure levels of DNA adducts. (elsevier.com)
  • Cells disrupted for rad5 are highly sensitive to this minor groove binding agent, and rad5 cells exhibit an in vivo adduct elimination defect indistinguishable from that seen in rad6 and rad18 cells as well as in NER-defective cells. (ucl.ac.uk)
  • 32-P-HPLC analysis of DNA adducts formed in vitro and in vivo by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline, utilizing an improved adduct enrichment procedure. (openrepository.com)
  • In vivo, three different adducts were found by NP1 enriched 32P-postlabeling in the liver of B[a]P-exposed rats. (maastrichtuniversity.nl)
  • Multiple DNA adducts specific to tobacco constituents have also been characterized for the first time in vitro or detected in vivo since 2012, and descriptions of those adducts are included. (umn.edu)
  • When a chemical binds to DNA, the DNA becomes damaged, and proper and complete replication cannot occur to make the normal intended cell. (wikipedia.org)
  • These results suggest that replication can switch from theta to RC mode after a replication fork is stalled by an MTase-DNA adduct. (aacrjournals.org)
  • Such replication-dependent DNA breaks may represent an important pathway that contributes to genome rearrangement and/or cytotoxicity. (aacrjournals.org)
  • Moreover, the interaction between CtIP and BRCA1, although dispensable for resection of endonuclease-generated DSB ends, is required for resection of Top2-adducted DSBs, as well as for cellular resistance to etoposide during genomic DNA replication. (rupress.org)
  • Topoisomerases facilitate DNA transactions such as replication and transcription by relieving DNA topological stress. (rupress.org)
  • These unprocessed Top2-DNA adducts block DNA replication and RNA transcription and generate lethal DSBs that can induce cell-death pathways. (rupress.org)
  • Erroneous replication of lesions in DNA by DNA polymerases leads to elevated mutagenesis. (rcsb.org)
  • If not repaired, these DNA adducts, particularly ICL lesions, can block transcription and DNA replication and cause cell death ( 6 ). (pubmedcentralcanada.ca)
  • During meiosis, two rounds of chromosome segregation occur after a single round of DNA replication, producing haploid progeny from diploid progenitors. (ebscohost.com)
  • In this application, we hypothesize that arylamine-induced repair and mutation is conformation-specific (S, B, W). We propose four major aims to help define adduct conformation and examine their specific effects on repair (initial damage recognition) and replication (replication fork heterogeneity). (grantome.com)
  • Specifically, these aims focus on: (1) conformation-specific repair in a human nucleotide excision repair (NER) system and long-range sequence effects, (2) damage recognition (protein-DNA interaction) (3) the thermodynamics of sequence-dependent slippage-induced frameshift mutagenesis, and (4) replication fork conformational heterogeneity and polymerase binding. (grantome.com)
  • Human RPA (replication protein A), a single-stranded DNA-binding protein, is required for many cellular pathways including DNA repair, recombination and replication. (elsevier.com)
  • The C-14 label enabled quantification of oxaliplatin-DNA adduct level with accelerator mass spectrometry (AMS). (aacrjournals.org)
  • Accelerator mass spectrometry (AMS) is currently the most sensitive method for trace DNA adduct detection. (le.ac.uk)
  • DNA isolation and sample preparation for quantification of adduct levels by accelerator mass spectrometry. (elsevier.com)
  • This work sought to measure Adriamycin-DNA adducts at sub-micromolar doses using accelerator mass spectrometry (AMS), a technique with origins in geochemistry for radiocarbon dating. (elsevier.com)
  • Phillips, Don R. / Detection of Adriamycin-DNA adducts by accelerator mass spectrometry at clinically relevant Adriamycin concentrations . (elsevier.com)
  • We present a meta-analysis to test the hypothesis that the presence of a high level of bulky DNA adducts in tissues is associated with an increased risk of cancer in humans. (aacrjournals.org)
  • All tissues examined except the breast had detectable adducts. (nih.gov)
  • Smokers and former smokers tended to have higher adduct levels than non-smokers in the tissues examined but this was only significant for the lung. (nih.gov)
  • Certain smokers had high adduct levels in all tissues examined, whilst in others high levels were only seen in some tissues. (nih.gov)
  • These results confirm the finding that cigarette smoking is associated with DNA damage in the lung and suggest that similar damage may be related to tobacco-induced neoplasms of other tissues. (nih.gov)
  • Experiments involving ethylene oxide (ETO) have been used to support the concept of using adducts in hemoglobin as a surrogate for DNA adducts in target tissues. (rti.org)
  • The loss of 7-HEG from DNA was both species and tissue dependent, with the adduct half-lives ranging from 2.9 to 5.8 days in rat tissues (brain, kidney, liver, lung, spleen, testis) and 1.0 to 2.3 days in all mouse tissues except kidney (t1/2 = 6.9 days). (rti.org)
  • only 1 out of 27 (4%) contained adduct in both tumor and surrounding tissues. (oup.com)
  • METHODS To investigate the notion that an underlying differential expression of phase I/II genes, and/or the presence of polycyclic aromatic hydrocarbon (PAH)-DNA adducts might explain the elevated PZ susceptibility, we examined prostate tissues (matched tissue sets consisting of PZ and TZ) from men undergoing radical retropubic prostatectomy for CaP (n = 26) or cystoprostatectomy (n = 1). (lancs.ac.uk)
  • This method has been used to reliably generate good yields of uncontaminated, pure DNA from animal and human tissues for analysis of adduct levels. (elsevier.com)
  • This method has been shown to be highly reproducible for the measurement of Adriamycin-DNA adducts in tumour cells in culture and can now be applied to the detection of these adducts in human tissues. (elsevier.com)
  • Among 5 smokers, for whom both bronchial and lymphocyte DNA was available, 7-methylguanine levels correlated in the two tissues (r = 0.77). (elsevier.com)
  • Detection of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine-DNA adducts in normal breast tissues and risk of breast cancer. (openrepository.com)
  • The DNA lesions derived from polycyclic aromatic compounds, inflammation-related reactive oxidizing species, and ultraviolet light result in the accumulation of malignant mutations that lead to a variety of human cancers. (nih.gov)
  • Ru( II )-complexes with polyazaaromatic ligands can undergo direct electron transfer with guanine nucleobases on blue light excitation that results in DNA lesions with phototherapeutic potential. (rsc.org)
  • Oxaliplatin-DNA adduct levels from PBMC correlated significantly to mean tumor volume change of evaluable target lesions (5 of the 6 patients had measurable disease). (aacrjournals.org)
  • In Escherichia coli cells, UvrABC repairs ICL lesions that cause DNA bending. (pubmedcentralcanada.ca)
  • The mechanisms and consequences of NER of ICL dG-MC-dG lesions that do not induce DNA bending remain unclear. (pubmedcentralcanada.ca)
  • The currently accepted hypothesis is that this protein recognizes the distortions/destabilization caused by DNA lesions rather than the lesions themselves. (elsevier.com)
  • The resulting XPC-RAD23B-DNA complexes serve as scaffolds for the recruitment of subsequent NER factors that lead to the excision of the oligonucleotide sequences containing the lesions. (elsevier.com)
  • Based on several well-known examples of DNA lesions like the UV radiation-induced CPD and 6-4 photodimers, as well as cisplatin-derived intrastrand cross-linked lesions, it is generally believed that the differences in excision activities in human cell extracts is correlated with the binding affinities of XPC-RAD23B to these DNA lesions. (elsevier.com)
  • This damaging system was used to induce numerous oxidative lesions including glyoxal DNA modifications, from which resulted a number of clones. (salford.ac.uk)
  • Barminomycin adducts were the most stable at 37 degrees C (no loss in the 48 h time frame studied) while carminomycin II and III lesions were least stable (each with a half-life of approximately 4-5 h). (edu.au)
  • The potential impact of such lesions on DNA methylation has received relatively little attention. (elsevier.com)
  • Utilizing an in vitro biochemical approach, it is shown that BPDE-derived DNA lesions can alter DNA methylation by prokaryotic MTases M.SssI and M.HhaI and mammalian MTase Dnmt3a at CpG and GCGC sites. (elsevier.com)
  • These effects depend on the conformational properties of the lesions and their positions within the DNA recognition sequence. (elsevier.com)
  • The critical role of DNA damage in cancer development makes it essential to develop highly sensitive and specific assays for DNA lesions. (geoscience.net)
  • The bifunctional alkylating anticancer drug nitrogen mustard forms a variety of DNA lesions, including monoadducts and intrastrand and interstrand crosslinks. (ox.ac.uk)
  • Structural evidence and adduct quantification were determined by selected reaction monitoring, based on the expected. (oup.com)
  • Structural evidence and adduct quantification were determined by selected reaction monitoring, based on the expected adduct ion [M+H + ] +1 , at m/z 435 with fragmentation to the product ion at m/z 319, and monitoring of the transition for the internal standard, m/z 444 → 328. (oup.com)
  • Quantification of phase I/II metabolizing enzyme gene expression and polycyclic aromatic hydrocarbon-DNA adduct levels in human prostate. (lancs.ac.uk)
  • Quantification of 3-nitrobenzanthrone-DNA adducts using online column-switching HPLC-electrospray tandem mass spectrometry. (openrepository.com)
  • The 06mdG adduct concentrations were much lower than those of N7mdG, ranging from non-detectable to 12.7 06mdG adducts/lO' deoxyguanosine nucleosides and many of the participants (40nS successfully analyzed) did not have detectable amounts of these adducts (limit of detection 0.03 06mdG adducts/l07 deoxyguanosine nucleosides). (cdc.gov)
  • A 32P-postlabeling method for the detection of adducts in the DNA of human fibroblasts exposed to sulfur mustard. (umassmed.edu)
  • This pure standard was used to determine detection limits of 1.4 pmoles of adduct using HPLC and liquid scintillation counting and 79 attomoles using AMS. (le.ac.uk)
  • Overall assay efficiency was calculated to be 29% and taking this into account the practical limit of detection for the 14C-postlabelling procedure was calculated to be 272 attomoles of adduct. (le.ac.uk)
  • The theoretical limit of detection was 3 adducts/1012 nucleosides, based on background 14C levels in blank HPLC fractions, which indicates the assay should ultimately be the most sensitive for detection of endogenous O6-MedG adducts in control human DNA. (le.ac.uk)
  • 1) We examined some previous methods for detection of albumin adduct using gas chromatography-mass spectrometry. (nii.ac.jp)
  • We analyzed bladder DNA from 27 cancer patients for dG-C8-4-aminobiphenyl (dG-C8-ABP) adducts using the liquid chromatography tandem mass spectrometry method with a 700 attomol (1 adduct in 10 9 bases) detection limit. (oup.com)
  • Previous detection has achieved a sensitivity of a few Adriamycin-DNA adducts/10 4 bp DNA, but has required the use of supra-clinical drug concentrations. (elsevier.com)
  • We have used conditions previously validated (by less sensitive decay counting) to extract [ 14 C]Adriamycin-DNA adducts from cells and adapted the methodology to AMS detection. (elsevier.com)
  • High-performance liquid chromatography (HPLC) with online radioactivity detection, the (32)P-HPLC (direct injection of the (32)P-labelled mixture into the HPLC with online (32)P-detection) method, gives both high sensitivity and good resolution of complex mixtures of DNA adducts. (openrepository.com)
  • We describe here ultrasensitive assays for DNA damage, which incorporate immuno-affinity with capillary electrophoresis (CE) separation and laser induced fluorescence (LIF) detection. (geoscience.net)
  • Results obtained by using an in vitro transcription system supplemented with eukaryotic topoisomerase I show that this inhibition can be attributed to physical blockage of the RNA polymerase by camptothecin-stabilized topoisomerase I-DNA complexes on the DNA template. (nih.gov)
  • Correlation between base-excision repair gene polymorphisms and levels of in-vitro BPDE-induced DNA adducts in cultured peripheral blood lymphocytes. (duke.edu)
  • In this study, we explored associations between genotypes of base-excision repair genes (PARP1 Val762Ala, APEX1 Asp148Glu, and XRCC1 Arg399Gln) and in vitro BPDE-induced DNA adducts in cultured peripheral blood lymphocytes in 706 cancer-free non-Hispanic white subjects. (duke.edu)
  • In vitro study showed DNA adduct after 3.61 min. (stackexchange.com)
  • A series of anthracyclines (comprising carminomycins I, II and III, and barminomycin) were tested for their ability to react with DNA to form site-specific adducts using an in vitro transcription assay. (edu.au)
  • abstract = "Limited sensitivity of existing assays has prevented investigation of whether Adriamycin-DNA adducts are involved in the anti-tumour potential of Adriamycin. (elsevier.com)
  • abstract = "Department of Health Risk Analysis and Toxicology, University of Maastricht, The Netherlands.32P-Postlabeling is a widely applied assay for the analysis of carcinogen-DNA adducts. (maastrichtuniversity.nl)
  • Nitropyrenes cause mutations (structural changes in DNA, the cell's genetic material) and are carcinogenic in some animals. (epa.gov)
  • Mutations may occur when inhaled nitropyrenes are metabolized to active derivatives that combine with DNA. (epa.gov)
  • When the investigators allowed the genes containing adducts to replicate, mutations occurred. (epa.gov)
  • To determine the relation between the location of DNA adducts and mutation, the investigators compared the regions in DNA where adducts formed to those regions where mutations occurred. (epa.gov)
  • 23 ) detected a high frequency of C:G to G:C transversion mutations at CpG islands in promotor regions after aza-dC treatment, suggesting that MTase-DNA adducts might be involved in mutagenesis. (aacrjournals.org)
  • We propose that DSBs resulted from NER of ICL dG-MC-dG adducts contribute to MC antitumor activity and mutations. (pubmedcentralcanada.ca)
  • Measurement of chromosomal aberrations, sister chromatid exchange, hprt mutations, and DNA adducts in peripheral lymphocytes of human populations at increased risk for cancer Morris, M. (ebscohost.com)
  • Hence we have quantified O 6 -MedG levels in a cross sectional study of patients with colorectal tumours to examine if DNA alkylation varies throughout the large bowel: previously, we reported on the association of K-ras mutations and the frequency of DNA alkylation in this population. (bmj.com)
  • If the damage is not repaired then when the cell replicates its DNA mistakes (mutations) are made that can lead to cancer. (elsevier.com)
  • However, the correlation between the observed p53 mutations, the AFB 1 DNA adducts and their activation pathways has not been elucidated. (elsevier.com)
  • Therefore, the differential expression of specific CYP450 genes in human hepatocytes can modulate the cytotoxicity, DNA adduct levels and frequency of p53 mutations produced by AFB 1 . (elsevier.com)
  • This adduct may alter the DNA conformation at critical stages of the replicative process, and cause mutations which initiate the carcinogenic process. (nyu.edu)
  • The depurination adducts were identified by HPLC and fluorescence line narrowing spectroscopy. (nih.gov)
  • At 8, 24, 48, and 168 hrs after dosing, the levels of DHP-derived DNA adduct in blood and liver were determined by 32 P-postlabeling/HPLC. (mdpi.com)
  • DNA was digested to nucleosides, fractionated by HPLC, and purified O 6 -MedG quantified by a radioimmunoassay. (bmj.com)
  • Accelerated (32)P-HPLC for bulky DNA adducts. (openrepository.com)
  • 32P-postlabeling of DNA adducts arising from complex mixtures: HPLC versus TLC separation applied to adducts from petroleum products. (openrepository.com)
  • Separation of 32P-labelled nucleoside 3',5'-bisphosphate adducts by HPLC. (openrepository.com)
  • A detailed kinetic analysis of the insertion and extension steps of dNTP incorporation in the vicinity of the adduct shows that both DNA polymerase beta (pol beta) and DNA polymerase eta (pol eta) catalyze translesion synthesis past oxaliplatin-GG adducts with greater efficiency than past cisplatin-GG adducts. (nih.gov)
  • Here we report the structure of a transcribing RNA polymerase II (pol II) complex stalled at a site-specific monofunctional pyriplatin-DNA adduct in the active site. (pnas.org)
  • DNA polymerase η (Pol-η) is a crucial polymerase that allows cancer cells to cope with the cisplatin-DNA adducts that are formed during chemotherapy. (rcsb.org)
  • DNA polymerase stalling, sister chromatid recombination and the BRCA genes. (ebscohost.com)
  • Two DNA restriction fragments containing either a d(GC)5 or a d(TTGCTTGATTAGTTGTGTT) insert were subjected to reaction with cis-diamminedichloroplatinum(II) and were then used as templates for RNA synthesis by T7 RNA polymerase. (cnrs-orleans.fr)
  • DNA adducts are a type of DNA damage. (wikipedia.org)
  • For example, mismatch repair proteins and some damage-recognition proteins bind to cisplatin-GG adducts with higher affinity than to oxaliplatin-GG adducts, and this differential recognition of cisplatin- and oxaliplatin-GG adducts is thought to contribute to the differences in cytotoxicity and tumor range of cisplatin and oxaliplatin. (nih.gov)
  • Furthermore, the observed differences in conformation provide a logical explanation for the differential recognition of cisplatin and oxaliplatin adducts by mismatch repair and damage-recognition proteins. (nih.gov)
  • In lung, bladder and pancreatic tissue a characteristic pattern of adducts was seen which has previously been reported as typical of cigarette-smoke-induced damage. (nih.gov)
  • R828112C046 How Do Chemicals in Diesel Engine Exhaust Damage DNA? (epa.gov)
  • Smokers with BLCA were found to have elevated levels of methylated metabolites, polycyclic aromatic hydrocarbons (PAHs), DNA adducts and DNA damage. (urotoday.com)
  • Collectively, the structure provides a basis for understanding how Pol-η in human cells can tolerate the DNA damage caused by cisplatin chemotherapy and offers a framework for the design of inhibitors in cancer therapy. (rcsb.org)
  • Overexpressing DNA repair activity mutant APE1 (226 + 177APE1), with only redox activity was ineffective suggesting it is the DNA repair function of APE1 and not its redox-signaling, that restores the Pt-damage removal. (sigmaaldrich.com)
  • Coffee consumption protects human lymphocytes against oxidative and 3-amino-1-methyl-5H-pyrido[4,3-b]indole acetate (Trp-P-2) induced DNA-damage: results of an experimental study with human volunteers. (semanticscholar.org)
  • Effects of instant coffee consumption on oxidative DNA damage, DNA repair, and redox system in mouse liver. (semanticscholar.org)
  • ii) mechanism of cellular DNA repair for UV-induced DNA damage. (iiarjournals.org)
  • The goal of this project is to understand how the cell repairs and replicates an important class of DNA damage. (elsevier.com)
  • This is the first report of the production of 6-oxo-M1dG in genomic DNA in intact cells and it has significant implications for understanding the role of inflammation in DNA damage, mutagenesis and repair. (vanderbilt.edu)
  • We have validated the potential of gdC as a marker of oxidative DNA damage and showed negligible cross-reactivity with 8-oxo-2'-deoxyguanosine or malondialdehyde-modified DNA as well as its utility in immunocytochemistry. (salford.ac.uk)
  • In the yeast Saccharomyces cerevisiae the RAD6 epistasis group defines a more poorly characterized set of DNA damage response pathways, believed to be distinct from NER. (ucl.ac.uk)
  • Therefore, they are of value in determining exposed or sensitive individuals or populations and in identifying agents that can induce DNA damage. (openrepository.com)
  • Human DNA is exposed to a variety of endogenous and environmental agents that may induce a wide range of damage. (geoscience.net)
  • Since the detected DNA adducts were not necessarily specific only for HCA, it is possible that HCA intake is a surrogate of other genotoxic substances, such as polycyclic aromatic hydrocarbons, in meat prepared at high temperatures. (openrepository.com)
  • Accurate characterization of carcinogenic DNA adducts using MALDI tandem time-of-flight mass spectrometry. (uncg.edu)
  • Two of the known carcinogenic DNA adducts, namely N-(2'-deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenyl-imidazo [4,5-b] pyridine (dG-C8-PhIP) and N-(2'-deoxyguanosin-8yl)-4-aminobiphenyl (dG-C8-ABP), were selected as our models. (uncg.edu)
  • Reactive metabolites may form specific DNA adducts and induce the tumors observed in mice. (rti.org)
  • UVC, may also induce production of ROS and DNA adducts, CPDs, which are repaired via the nucleotide excision repair (NER) pathway ( 7 ). (iiarjournals.org)
  • Can DNA methylation induce breast cancer? (stackexchange.com)
  • When rats were fed either beef or chicken, three types of DNA adducts in colon tissue were significantly higher after consumption of beef than after consumption of chicken. (wikipedia.org)
  • We have recently solved the solution structure of the oxaliplatin-GG adduct and have shown that it is significantly different from the previously published solution structures of the cisplatin-GG adducts. (nih.gov)
  • DNA methyltransferase 1 (DNMT1) expression was significantly higher in smokers than non-smokers with BLCA. (urotoday.com)
  • Results PBMC from TFW showed significantly higher levels of DNA adducts compared with referents. (bmj.com)
  • We found that levels of BPDE-induced DNA adducts were significantly higher in ever smokers than in never smokers and that individuals with the Glu variant genotypes (i.e. (duke.edu)
  • IS DNA yield did not differ significantly at the three time points [overall (mean of three extractions) DNA yield, 66 +/- 20 mu g]. (maastrichtuniversity.nl)
  • Adduct levels in IS at each time point were higher than those in PBL, leading to a significantly higher overall (mean of three quantifications) level of adducts in IS than PBL (3.3 +/- 0.2 versus 2.1 +/- 0.1/10s nt, P = 0.02). (maastrichtuniversity.nl)
  • Total HCA intake (r = 0.33, P = 0.03), consumption of fried meat (r = 0.39, P = 0.01), beef (r = 0.32, P = 0.03) and processed meat (r = 0.51, P = 0.0004) were statistically significantly correlated with the level of DNA adducts in breast tissue. (openrepository.com)
  • Again, DNA adduct levels were significantly higher using salting out as compared to phenol extraction for the adduct which comigrated with the BPDE-DNA adduct standard (adduct 1) and an unknown adduct (adduct 2). (maastrichtuniversity.nl)
  • Residence in southern European countries, higher maternal body mass index, delivery by cesarean section, male infant sex, low maternal intake of fruits rich in vitamin C, high intake of dairy products, and low adherence to healthy diet score were statistically significantly associated with higher adduct levels in adjusted models. (ku.dk)
  • Six studies measured adducts in WBCs and one in normal lung tissue around tumor tissue. (aacrjournals.org)
  • Despite some methodological limitations, our meta-analysis shows that current smokers with high levels of adducts have an increased risk of lung and bladder cancers. (aacrjournals.org)
  • Purified DNA from human lung, liver, bladder, pancreas, breast and cervix has been analysed for DNA adducts using the nuclease P1 modification of the 32P post-labelling technique. (nih.gov)
  • DNA adduct profiles differed quantitatively and qualitatively in liver, total lung, and enriched lung cell fractions. (rti.org)
  • In both rat and mouse lung, HPEG was the major adduct at 1 per 108 bases at 0 h, and these levels halved at 42 h. (rti.org)
  • In both rat Type II and non-Type II cells, HPEG was the major adduct and was about three times higher in Type II cells than in total lung. (rti.org)
  • For mice, DNA adduct levels in Clara cells and non-Clara cells were similar to total lung. (rti.org)
  • The results of our pooled and meta-analyses suggest that bulky DNA adducts are associated with lung cancer arising in current smokers after a follow-up of several years. (ccceh.org)
  • The area under the curve (AUC) for BPDE-DNA adducts in lung was 29.5% less (P = 0. (eurekamag.com)
  • The results of this study support the hypothesis that BITC inhibits B[a]P-induced lung tumorigenesis in A/J mice by inhibiting the metabolic activation of B[a]P to BPDE-DNA adducts. (eurekamag.com)
  • The major 3-NBA-derived DNA adduct formed in rat lung cochromatographed with dG3′p-N2-ABA in two independent systems (thin layer and high-performance liquid chromatography). (ovid.com)
  • The levels of hydrophobic DNA adducts in non-tumorous lung tissue of 55 of the patients were analyzed by the 32 P-postlabelling assay. (oup.com)
  • Although small yet repeatable signals were also detected in lung DNA from rats treated for 3 days with tobacco smoke. (elsevier.com)
  • Analysis of cellular DNA from A549 human lung carcinoma cells that were incubated with low doses of BPDE (32 nM-1 muM) showed a clear dose-response relationship. (geoscience.net)
  • 29 coke oven workers and a standardised control group were investigated for frequencies of DNA single strand breakage, DNA protein cross links (alkaline filter elution assay), sister chromatid exchange, and DNA adducts ({sup}32{end}P postlabeling assay) in lymphocytes. (ebscohost.com)
  • The techniques developed for this assay were utilised to quantitate O6-MedG adducts formed in DNA exposed to 14C-S-adenosylmethionine. (le.ac.uk)
  • A recently developed 32 P-postlabeling assay was applied with anion exchange chromatography as an adduct enrichment method. (elsevier.com)
  • We investigated the applicability of induced sputum (IS), a non-invasive derivative from the lower respiratory tract, for smoking-related DNA adduct analysis and its comparability with peripheral blood lymphocytes (PBL), Lipophilic DNA adducts were quantified by the P-32-post-labeling assay in IS and PBL of smokers (n = 9) with stable smoking status at three time points tone week intervals) and nonsmokers (n = 9) at one time point. (maastrichtuniversity.nl)
  • The detected DNA adducts could not be confirmed to be specific HCA-derived DNA adducts by comparison with external standards, using the (32)P-postlabelling assay. (openrepository.com)
  • 32P-Postlabeling is a widely applied assay for the analysis of carcinogen-DNA adducts. (maastrichtuniversity.nl)
  • Optimization of most steps in this assay has been given attention, but influences of DNA isolation and DNA purity on adduct quantitation have not been investigated systematically. (maastrichtuniversity.nl)
  • A fluorescently labeled oligonucleotide containing a single BPDE adduct was synthesized and used as a fluorescent probe for competitive assay. (geoscience.net)
  • For non-competitive assay, a fluorescently labeled secondary antibody fragment F(ab')2 was used as an affinity probe to recognize a primary antibody that was specific for the BPDE-DNA adducts. (geoscience.net)
  • The assay was used for the determination of trace levels of BPDE-DNA adducts in human cells. (geoscience.net)
  • The cytotoxicity of platinum compounds is thought to be determined primarily by their DNA adducts. (nih.gov)
  • These adducts have been suggested to cause chromosomal rearrangements and contribute to cytotoxicity, but the detailed mechanisms have not been elucidated. (aacrjournals.org)
  • This aflatoxin-DNA adduct excretion product serves as a biomarker of the biologically effective dose of aflatoxin, and elevated levels are associated with increased risk of liver cancer. (pnas.org)
  • Identification and quantitation of the depurination and stable DNA adducts of 7,12-dimethylbenz[a]anthracene (DMBA) formed by cytochrome P450 in rat liver microsomes previously established one-electron oxidation as the predominant mechanism of activation of DMBA to bind to DNA. (nih.gov)
  • B[a]P. The lacZ mutants were recovered by packaging of DNA isolated from liver into lambda phage, and expressed in E. coli C lacZ- recA-galE- bacteria. (tudelft.nl)
  • Several other, unidentified adducts were present at two to three times higher concentrations in mouse, but not in rat liver. (rti.org)
  • Total GST activity and adducts of malondialdehyde with DNA (M 1 G), which reflect endogenous lipid peroxidation, were measured in colon mucosa, liver, and blood leukocytes. (aacrjournals.org)
  • Similar results were obtained in liver DNA. (eurekamag.com)
  • BP administration to rats produced BPDE-DNA adducts in both liver and lungs. (elsevier.com)
  • These adducts were a type of methyl-cytosine (possibly N3-methyl-cytosine), an adduct of two malondialdehyde molecules with guanine, and carboxyl-adenine. (wikipedia.org)
  • The primary endpoint was modulation of levels of aflatoxin-N 7 -guanine adducts in urine samples collected 3 months into the intervention measured by using sequential immunoaffinity chromatography and liquid chromatography-electrospray mass spectrometry. (pnas.org)
  • The depurination adducts, which constitute 99% of all the adducts detected, are DMBA bound at the 12-methyl group to the N-7 of adenine or guanine, namely, 7-methylbenz[a]anthracene (MBA)-12-CH2-N7Ade and 7-MBA-12-CH2-N7Gua. (nih.gov)
  • The three-stage pathway, involving mEH, forming the ultimately reactive species BPDE that binds to guanine to form the dG- N 2 -BPDE adduct (adduct 1) is shown on the right. (springer.com)
  • Binding of an organo-osmium anticancer complex not only to guanine but also cytosine on DNA is revealed by electron-detachment dissociation tandem MS. (rsc.org)
  • A bulky cationic cobalt( III ) porphyrin carrying two water molecules as axial ligands interacts in a π-stacking like mode with the 5′-external guanine quartet of G-quadruplex DNA. (rsc.org)
  • The pyrenyl chromophores of the BPDE adducts, linked by the C10 atom to the exocyclic nitrogen of guanine, interact in the photoexcited state, as evidenced by excimer fluorescence. (chalmers.se)
  • Current smokers showed a statistically significant difference between cases and controls, with cases having 83% higher levels of adducts than controls (95% confidence interval, 0.44-1.22). (aacrjournals.org)
  • There appeared to be considerable variation in adduct levels among smokers which could not be accounted for by duration or daily consumption level. (nih.gov)
  • The bronchial DNA adduct levels in smokers were statistically higher than those in non-smokers. (elsevier.com)
  • There was no significant difference in total cell count, cell viability, squamous cell count and DNA yield between smokers and non-smokers. (maastrichtuniversity.nl)
  • A typical smoking-associated diagonal radioactive zone was observed in the adduct maps of IS and PBL of all and five smokers, respectively, and of none of the non-smokers. (maastrichtuniversity.nl)
  • Lipophilic DNA adduct levels in both IS and PBL of smokers were higher than those of non-smokers (3.7 +/- 0.9 versus 0.7 +/- 0.2/10(8) nt, P = 0.0005, and 2.1 +/- 0.3 versus 0.6 +/- 0.1/10(8) nt, P = 0.0001, respectively). (maastrichtuniversity.nl)
  • Occupational nitrosamine exposures from a rubber vehicle seal (VS) curing operation were compared with the peripheral blood lymphocyte concentrations of two nitrosamine-related DNA adducts. (cdc.gov)
  • Methods TFW (n=69) and referents (n=69) were investigated for bulky DNA adducts (by 32 P-postlabelling) and expression of microRNAs (miRNAs) (by small RNA sequencing) in peripheral blood mononuclear cells (PBMC), as well as circulating free arachidonic acid (AA) and eicosanoid profiles in plasma (by liquid chromatography-tandem mass spectrometry). (bmj.com)
  • 7-methylguanine DNA adducts were determined in macroscopically normal bronchial specimens and peripheral blood lymphocytes of 20 patients undergoing pulmonary surgery. (elsevier.com)
  • BPDE-DNA adducts detected in human pulmonary alveolar macrophages were related to current smoking habits, in contrast to the adducts found in peripheral blood leukocytes. (elsevier.com)
  • It was the aim of this study to examine the association of the consumption of meat in general, meat prepared by different cooking methods and the dietary intake of heterocyclic aromatic amines (HCA) with the level of DNA adducts in the breast tissue of women undergoing reduction mammoplasty. (openrepository.com)
  • Levels of DNA adducts were also related to smoking habits. (bmj.com)
  • This is also the major adduct formed in tissue of rats or mice treated with 3-aminobenzanthrone (3-ABA), the major human metabolite of 3-NBA. (ovid.com)
  • The DNA isolation method described is based upon digestion of tissue with proteinase K, followed by extraction of DNA using Qiagen isolation columns. (elsevier.com)
  • Dietary intake of meat and meat-derived heterocyclic aromatic amines and their correlation with DNA adducts in female breast tissue. (openrepository.com)
  • DNA adduct analysis in breast tissue was performed by (32)P-postlabelling analysis. (openrepository.com)
  • Spearman rank correlation coefficients (r) were calculated to examine the association of meat consumption and dietary HCA intake with tissue DNA adduct levels. (openrepository.com)
  • We observed strong correlations of dietary HCA intake and consumption of fried and processed meat with DNA adduct levels in breast tissue of 44 women. (openrepository.com)
  • Identification and quantitation of 7,12-dimethylbenz[a]anthracene-DNA adducts formed in mouse skin. (nih.gov)
  • In this paper we report the identification and quantitation of the depurination and stable DMBA-DNA adducts formed in mouse skin. (nih.gov)
  • Sun, X. Ultrasensitive UPLC-MS-MS Method for the Quantitation of Etheno-DNA Adducts in Human Urine. (mdpi.com)
  • The ternary complex of BPDE-DNA adducts with the bound antibodies was separated from the unbound antibodies using CE and detected with LIF for quantitation of the DNA adducts. (geoscience.net)
  • NEW YORK (GenomeWeb) - Alkylating substances such as tobacco smoke and environmental toxins can create mutagenic alkylguanine DNA adducts. (genomeweb.com)
  • The latter adduct, in particular, may be important in the mutagenic as well as the cytotoxic activity of DTIC. (tudelft.nl)
  • BPDE reacts with DNA to form principally the pre-mutagenic adduct 10-(deoxyguanosin- N 2 -yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydro-BaP (dG- N 2 -BPDE) (Arlt et al. (springer.com)
  • These goals will be examined in two specific aims: (1) to determine the polymerases involved in accurate and mutagenic bypass of O2-POB-dT and (2) to determine the mechanisms by which the POB-adducts are repaired. (elsevier.com)
  • Mass spectrometry (MS) is used in this study to measure DNA adducts and linked to a chromatographic system, such as gas chromatography (GC). (healtheffects.org)
  • A common method to measure DNA adducts is through DNA hydrolysis, adduct enrichment, (32)P-post-labelling and chromatographic separation. (openrepository.com)
  • Mass spectrometry is a powerful technique because it can distinguish among different carcinogen-DNA adducts, and it provides information about chemical structure. (healtheffects.org)
  • The goal of this study is to explore the use of matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS) to determine the identity of carcinogen-DNA adducts. (uncg.edu)
  • Hemoglobin (Hb) 4-aminobiphenyl (4-ABP) adduct levels were measured by gas chromatography-mass spectrometry. (oup.com)
  • ELISA unequivocally showed Ab recognition toward gdC, which was confirmed by gas chromatography-mass spectrometry of the derivatized adduct after formic acid hydrolysis to the modified base. (salford.ac.uk)
  • By 32P-postlabelling analysis using an alkenylbenzene solvent system the amount of B[a]P-DNA adducts was lower in mice fed the eugenol diet than in mice fed the control diet but the decrease was not statistically significant. (tudelft.nl)
  • The concentrations of HEtVal were similar in concurrently exposed rats and mice, whereas DNA from rats had at least 2-fold greater concentrations of 7-HEG than DNA from mice. (rti.org)
  • Balb/c mice were immunized with DNA, oxidatively modified by UVC/hydrogen peroxide in the presence of endogenous metal ions. (salford.ac.uk)
  • Further investigation revealed that topical pretreatment(s) of mice with PBP 1-5 (200 μg/day × 4) resulted in a significant decrease in the levels of single topical B( a )P (1 mg/mouse) - induced DNA adducts in epidermal DNA determined by employing 32 P-post labeling analysis. (begellhouse.com)
  • The approaches developed provide unique structural and polarity information on tetrols and BPDE-DNA adducts. (osapublishing.org)
  • The BPDE-DNA adducts present in the sample or standard are probed with an Anti-BPDE-I Antibody, followed by an HRP Conjugated Secondary Antibody. (cellbiolabs.com)
  • The stable DNA adducts were analyzed by the 32P-postlabeling method. (nih.gov)
  • The amount of stable DNA adducts observed with denatured DNA was 70% lower in the HRP system and 30% lower in the microsomal system compared to native DNA. (nih.gov)
  • Hydroxylation of the alpha carbons yields 2 reactive species, which alkylate DNA to produce pyridyloxobutyl (pob)-DNA or methyl-DNA adducts. (aacrjournals.org)
  • In molecular genetics, a DNA adduct is a segment of DNA bound to a cancer-causing chemical. (wikipedia.org)
  • However, the detailed molecular mechanism by which cells process DNA modified by pyriplatin and related monofunctional complexes is not at all understood. (pnas.org)
  • In a view to develop new DNA alkylating antitumour drugs, evaluating the precise mechanism of action and the molecular/cellular consequences of the alkylation is a point of major interest. (biochemj.org)
  • Successful completion of the proposed aims will help us gain a better grasp on the protein-DNA interactions involved in human NER and trans-lesion synthesis, which have important implications for resolving the molecular details of cancer etiology. (grantome.com)
  • The key molecular players (adduct structures, polymerases, repair proteins) producing adverse outcomes must be identified, characterized, and understood in order to devise appropriate prevention and risk assessment strategies. (grantome.com)
  • We have carried out an extensive molecular mechanics/energy minimization search to locate feasible structures for the major MeIQx adduct in DNA, using the sequence d(5′-C1-G2-C3-G4[IQ]-C5-G6-C7-3′)· d(5′-G8-C9-G10-C11-G12-C13-G14-3′) with MeIQx modification at G4. (nyu.edu)
  • APE1, the DNA base excision repair protein, regulates the removal of platinum adducts in sensory neuronal cultures by NER. (sigmaaldrich.com)
  • Earthworm testis cells were treated with a combination of 5 mM hydroxyurea plus 50 μM cytosine-β-D-arabinofuranoside for 6 h to block DNA rejoining capacity and to investigate excision dynamics. (iiarjournals.org)
  • The relationships between XPC binding to conformationally diverse DNA adducts and their excision by the human NER system: Is there a correlation? (elsevier.com)
  • Geacintov, Nicholas E. / The relationships between XPC binding to conformationally diverse DNA adducts and their excision by the human NER system : Is there a correlation? . (elsevier.com)
  • Nucleotide excision repair (NER) is the primary pathway for the removal of DNA adducts that distort the double helix. (ucl.ac.uk)
  • Excision repair of nitrogen mustard-DNA adducts in Saccharomyces cerevisiae. (ox.ac.uk)
  • Although it is known that nucleotide excision repair (NER) is important in processing these adducts, the role of the other principal excision repair pathway, base excision repair (BER) is less well defined. (ox.ac.uk)
  • The pH-dependence curves of excision of eC, HEC and HPC by Mug are bell shaped and the most efficient excision of adducts occurs within the pH range of 8.6-9.6. (unibas.ch)
  • The observed increase of excision of HEC and HPC above pH 7.2 can be explained by deprotonation of these adducts, which are high pK(a) compounds and exist in a protonated form at neutrality. (unibas.ch)
  • In the present study, the major BP diol epoxide adduct in DNA, BP-N(2)-deoxyguanosine (BP-dG), was placed at a template-primer junction. (rcsb.org)
  • In animal experiments, PAH-DNA adduct levels explained tumor outcome. (aacrjournals.org)
  • The results of these studies suggest that B[a]PDE may initiate cancer not only by genotoxic mechanisms, but might also contribute to tumor development by epigenetic effects that involve changes in DNA methylation status. (elsevier.com)
  • Our laboratory has shown that 3-(2-deoxy-β-D-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) is the most abundant DNA adduct formed from the lipid peroxidation product, malondialdehyde, or the DNA peroxidation product, base propenal. (vanderbilt.edu)
  • Exocyclic adducts of DNA bases, such as etheno- and hydroxyalkano- ones, are generated by a variety of bifunctional agents, including endogenously formed products of lipid peroxidation. (unibas.ch)
  • Clinically, carcinogen-DNA adducts have been linked to various cancer diseases. (uncg.edu)
  • Tockman, M. S. / Determination of carcinogen-DNA adducts by immunoassay . (elsevier.com)
  • We have previously shown that arylamine adducts in DNA exist in three well-defined conformations: stacked (S), external B-type (B), and wedge (W). The conformation depends on the location of the carcinogen moiety in the DNA molecule, and the population ratios of the types under physiological conditions are sequence-dependent. (grantome.com)
  • Influences of DNA isolation and RNA contamination on carcinogen-DNA adduct analysis by P-32-postlabeling. (maastrichtuniversity.nl)
  • However, the DNA adducts are differentially recognized by a number of cellular proteins. (nih.gov)
  • The ability of these cellular proteins to discriminate between cisplatin and oxaliplatin adducts suggest that there exist significant conformational differences between the adducts, yet the crystal structures of the cisplatin- and oxaliplatin-GG adducts were very similar. (nih.gov)
  • The resulting adducts interfere with key cellular processes, such as transcription, to trigger downstream events responsible for drug activity. (pnas.org)
  • Regarding the multiple roles of GAPDH in apoptosis and DNA repair, the cytotoxic and apoptotic activities of GAPDH were evaluated and present opposite effects in two different cellular models. (biochemj.org)
  • Chronic inflammation results in increased production of reactive oxygen species (ROS), which can oxidize cellular molecules including lipids and DNA. (vanderbilt.edu)
  • Our results strongly suggest that earthworms seem to be efficient at repairing H 2 O 2 -induced oxidative DNA adducts, but not so capable of removing UV-induced pyrimidine dimers from their genome. (iiarjournals.org)
  • Nuclear oxidation of a major peroxidation DNA adduct, M1dG, in the Genome. (vanderbilt.edu)
  • The methylation of DNA at CpG dinucleotides by DNA methyltransferases (MTases) is an epigenetic alteration of the genome that plays an important role in the regulation of gene expression in eukaryotes. (elsevier.com)
  • Comparison of the rates of repair in this gene with those in a different genomic region indicate that the contributions of NER and BER to the repair of nitrogen mustard adducts may not be the same genome wide. (ox.ac.uk)
  • Release of sulfur mustard-modified DNA bases by Escherichia coli 3-methyladenine DNA glycosylase II. (umassmed.edu)
  • The tetrols intercalated between the DNA bases showed quite different fluorescence spectra compared to tetrols not complexed with DNA. (osapublishing.org)
  • Psoralen intercalates into the DNA double helix where it is ideally positioned to form one or more adducts with adjacent pyrimidine bases, preferentially thymine, upon excitation by an ultraviolet photon. (wikipedia.org)
  • This indicated that the stacking between the BPDE adduct and its neighbouring ssDNA bases had been disrupted and there was a lack of substantial direct contacts between the protein residues and the lesion itself. (elsevier.com)
  • Cisplatin and oxaliplatin are structurally distinct, but form the same types of adducts at the same sites on DNA. (nih.gov)
  • Thus, the greater efficiency of bypass of oxaliplatin-GG adducts by pol eta may explain the lower mutagenicity of oxaliplatin compared to cisplatin. (nih.gov)
  • Cisplatin causes renal DNA adducts and oxidative stress in rodents. (aspetjournals.org)
  • Tobacco smoking, on the other hand, caused a significant increase of the levels of PAH-DNA adducts but did not affect 1-OHpyrene values. (tudelft.nl)
  • Relationship between polycyclic aromatic hydrocarbon-DNA adducts, environmental tobacco smoke, and child development in the World Trade Center cohort. (umassmed.edu)
  • PUBLIC HEALTH RELEVANCE: One way by which tobacco smoke causes cancer is by damaging the DNA in the cell. (elsevier.com)
  • In the present study, we have systematically examined the binding of RPA to a battery of well-defined ssDNA (single-stranded DNA) substrates using fluorescence spectroscopy. (elsevier.com)
  • Strong BPDE excimer fluorescence is observed in the alternating poly(dGdC).poly(dGdC) sequence, whereas it is weak in the homopolymeric poly(dG).poly(dC) and in calf thymus DNA. (chalmers.se)
  • No excimer fluorescence is observed for the BPDE adducts in poly(dAdC).poly(dGdT) or poly(dAdG).poly(dCdT). (chalmers.se)
  • BACKGROUND: Bulky DNA adducts reflect genotoxic exposures, have been associated with lower birth weight, and may predict cancer risk. (ku.dk)
  • Sequestering of the hydrophobic BP adduct in this new substrate-binding site permits the DNA to exhibit normal geometry for primer extension. (rcsb.org)
  • Postlabelling of DNA isolated from the biopsies was used to determine the spectrum of hydrophobic adducts present. (eurekamag.com)
  • We have investigated gender differences in the p 53 mutational spectrum and levels of hydrophobic DNA adducts. (oup.com)
  • Methods: We pooled 11 studies (3,600 subjects) in which bulky DNA adducts were measured in human white blood cells with similar 32P-postlabeling techniques and for which a similar set of variables was available, including individual data on age, gender, ethnicity, batch, smoking habits, BMI, and season of blood collection, and a limited set of gene variants. (ccceh.org)
  • The oligonucleotides carrying adducted cytosines were studied as substrates of Escherichia coli Mug, human TDG and fission yeast Thp1p glycosylases. (unibas.ch)
  • In the productive structures, the bulky adduct is flipped/looped out of the DNA helix into a structural gap between the little finger and core domains. (rcsb.org)
  • With a fluorescent base-stacking bulky adduct, (+)-cis-anti-BPDE-dG, we demonstrated that, on binding of RPA. (elsevier.com)
  • The objective of the present study was to identify proteins involved in the recognition and mechanism of action of S23906-DNA adducts. (biochemj.org)
  • Workers from all three of these locations had detectable concentrations of N7mdG adducts, ranging from 0.1 to 133.2 adducts/l07 deoxyguanosine nucleosides. (cdc.gov)
  • For example, the term "DMBA-DNA adduct" in a scientific journal refers to a piece of DNA that has DMBA attached to it. (wikipedia.org)
  • We hypothesize that the enzyme structure undergoes a pH-induced rearrangement allowing the participation of Lys68 of Mug in catalysis via a hydrogen bond interaction of its epsilon-amino group with N(4) of the cytosine exocyclic adducts. (unibas.ch)
  • Voltammetric behaviour of chemical-activated MC in the presence of native DNA confirms existence of DNA-MC interactions that lead to different adducts after every kind of activation. (jbsdonline.com)
  • In conclusion, voltammetric techniques are capable of distinguishing between different adducts and they are therefore a very simple and valuable alternative to studying DNA interactions with substances of biological interest. (jbsdonline.com)
  • The DNA sequence specificity of all anthracyclines was similar (the most intense binding sites being 5'-GC sequences), although barminomycin was the most selective for 5'-GC. (edu.au)