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)Smoking-related dna adducts: P-postlabeling analysis of 7-methylguanine in human bronchial and lymphocyte dna<...
Lifestyle, Environmental, and Genetic Predictors of Bulky DNA Adducts in a Study Population Nested within a Prospective Danish...
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Products
DNA adduct
DNA adducts are researched in laboratory settings. A typical experimental design for studying DNA adducts is to induce them ... forming DNA adducts, and inducing double-strand breaks (DSBs). In regards to DNA adduct formation, this analysis was conducted ... Ongoing research on DNA adducts seeks to overcome these complications. It is the hope that in future medical practices DNA ... In molecular genetics, a DNA adduct is a segment of DNA bound to a cancer-causing chemical. This process could lead to the ...
Mitosene
"Mitosene-DNA Adducts. Characterization of Two Major DNA Monoadducts Formed by 1,10-Bis(acetoxy)-7-methoxymitosene upon ...
Glycidamide
... reacts with DNA to form adducts. It is more reactive toward DNA than acrylamide. Several glycidamide-DNA adducts ... The main DNA adducts are N7-(2-carbamoyl-2-hydroxyethyl)-guanine (or N7-GA-Gua) and N3-(2-carbamoyl-2-hydroxyethyl)adenine (or ... Mice and rats show mutations and DNA adducts consistent with those arising from glycidamide. Another study found tumors in the ... ISBN 978-1-4419-3672-1. Bergmark, E., Calleman, C. J., & Costa, L. G. (1991). Formation of hemoglobin adducts of acrylamide and ...
Eicosanoid
LTA4 can form adducts with tissue DNA. Other reactions of lipoxygenases generate cellular damage; murine models implicate 15- ... PGs and LTs may signal or regulate DNA-transcription there; LTB4 is ligand for PPARα.(See diagram at PPAR). Both COX1 and COX2 ...
Tobacco smoking
Liu XY, Zhu MX, Xie JP (2010). "Mutagenicity of acrolein and acrolein-induced DNA adducts". Toxicol. Mech. Methods. 20 (1): 36- ... Tompkins EM, McLuckie KI, Jones DJ, Farmer PB, Brown K (2009). "Mutagenicity of DNA adducts derived from ethylene oxide ... Kastan MB (2008). "DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture". Mol ... The most important chemicals causing cancer are those that produce DNA damage, since such damage appears to be the primary ...
Smoking
Liu XY, Zhu MX, Xie JP (2010). "Mutagenicity of acrolein and acrolein-induced DNA adducts". Toxicol. Mech. Methods. 20 (1): 36- ... Tompkins EM, McLuckie KI, Jones DJ, Farmer PB, Brown K (2009). "Mutagenicity of DNA adducts derived from ethylene oxide ... Kastan MB (2008). "DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture". Mol ... The most important chemicals causing cancer are those that produce DNA damage since such damage appears to be the primary ...
Cigarette
Liu XY, Zhu MX, Xie JP (2010). "Mutagenicity of acrolein and acrolein-induced DNA adducts". Toxicol. Mech. Methods. 20 (1): 36- ... Tompkins EM, McLuckie KI, Jones DJ, Farmer PB, Brown K (2009). "Mutagenicity of DNA adducts derived from ethylene oxide ... Kastan MB (2008). "DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture". Mol ... The most important chemical compounds causing cancer are those that produce DNA damage since such damage appears to be the ...
Crosslinking of DNA
CG adduct destabilizes the helix and induces a bend and twist in the DNA. DNA crosslinking lesions can also be formed when ... intrastrand DNA crosslinks, interstrand DNA crosslinks, and DNA-protein crosslinks. When cisplatin generates DNA crosslinks, it ... Cancer treatments have been engineered using DNA cross-linking agents to interact with nitrogenous bases of DNA to block DNA ... These adducts result in local distortions to DNA at the site of intercalation. Psoralens are used in the medical treatment of ...
4-Aminobiphenyl
... causes DNA damage, which is thought to be mediated by formation of DNA adducts. In this process, 4- ... A linear correlation was found between adduct levels and the occurrence of liver tumors in female mice by comparing DNA adducts ... The compound can be metabolized by humans which the product may form adducts with DNA in human urothelial mucosa and bladder ... The final products of this metabolism are aryl nitrenium ions which form DNA adducts. During this process reactive oxygen ...
Adduct
... ions are often formed in a mass spectrometer ion source. Adductomics DNA adduct IUPAC, Compendium of Chemical ... Adducts often form between Lewis acids and Lewis bases. A good example is the formation of adducts between the Lewis acid ... Adducts are not necessarily molecular in nature. A good example from solid-state chemistry is the adducts of ethylene or carbon ... An adduct ion is formed from a precursor ion and contains all of the constituent atoms of that ion as well as additional atoms ...
Phenanthriplatin
... forms monofunctional adducts with guanosine residues in the DNA. The large and hydrophobic nature of the ... "Effect of a Monofunctional Phenanthriplatin-DNA Adduct on RNA Polymerase II Transcriptional Fidelity and Translesion Synthesis ... a major protein used by the cell to transcribe DNA. Since transcription is essential for DNA synthesis and gene expression, ... A study examining the effects of monofunctional adducts on bacterial growth reported a significant decrease in Escherichia coli ...
Adductomics
... is the study of DNA adducts in the context of an entire genome. DNA adducts are compounds that bind to DNA, causing ... "DNA adductome strategy for detection of multiple DNA adducts." Nippon Kankyo Hen'igen Gakkai Taikai Puroguramu, Yoshishu. 34:77 ... The science of adductomics seeks to identify all DNA adducts and the target sequence of each adduct. The term "adductome" first ... Although originally the term related to adducts of DNA, the adductomic approach has now been adopted by protein chemists in ...
Indeno(1,2,3-cd)pyrene
These groups can ultimately form an adduct with the base of a nucleotide in the DNA. DNA adducts with PAHs can disrupt the DNA ... Baird, W. M.; Hooven, L. A.; Mahadevan, B. (2015). "Carcinogenic polycyclic aromatic hydrocarbon-DNA adducts and mechanism of ... replication or modify the DNA, by removing bases like adenine and guanine from the nucleotides. This can in the end lead to ...
Molecular lesion
A DNA adduct is a segment of DNA that binds to a chemical carcinogen. Some adducts that cause lesions to DNA included ... MDA reacts with DNA to form the M1dG adduct which causes DNA lesions. Many systems are in place to repair DNA and RNA lesions ... ROS is one of the major endogenous sources of DNA damage and the most studied oxidative DNA adduct is 8-oxo-dG. Other adducts ... These epoxy aldehydes can damage DNA by producing etheno adducts. An increase in this type of DNA lesion exhibits conditions ...
Deborah Zamble
DNA Adducts by the Mammalian Excision Nuclease". Biochemistry. 35 (31): 10004-10013. doi:10.1021/bi960453+. ISSN 0006-2960. ... "HMG-domain proteins specifically inhibit the repair of the major DNA adduct of the anticancer drug cisplatin by human excision ... "Cisplatin and DNA repair in cancer chemotherapy". Trends in Biochemical Sciences. 20 (10): 435-439. doi:10.1016/S0968-0004(00) ...
Polycyclic aromatic hydrocarbon
Stable adducts may lead to DNA replication errors, while unstable adducts react with the DNA strand, removing a purine base ( ... These metabolites can bind to DNA at specific sites, forming bulky complexes called DNA adducts that can be stable or unstable ... This enzyme then metabolically processes the PAHs to quinone metabolites that bind to DNA in reactive adducts that remove ... Baird, W. M.; Hooven, L. A.; Mahadevan, B. (2015-02-01). "Carcinogenic polycyclic aromatic hydrocarbon-DNA adducts and ...
Sudan I
... reacts with DNA in vitro. The major DNA adduct formed in this reaction is identified as the 8-(phenylazo)guanine adduct, which ... Guanosine DNA adducts derived from peroxidase metabolites of Sudan 1 were also found in vivo in the bladder of rats. The ... As a consequence DNA, RNA and protein adducts are formed. (See figure 2). Therefore, peroxidase-catalyzed activation of Sudan I ... Hence, formation of adducts of Sudan I reactive species with nucleophilic species, such as DNA, tRNA, proteins, polynucleotides ...
Liver disease
... which can damage DNA). The level of oxidative stress and acetaldehyde-induced DNA adducts due to alcohol consumption does not ... Oxidative DNA damage is mutagenic and also causes epigenetic alterations at the sites of DNA repair. Epigenetic alterations and ... "Formation of acetaldehyde-derived DNA adducts due to alcohol exposure". Chemico-Biological Interactions. 188 (3): 367-75. doi: ... The excess deoxycholic acid causes DNA damage and inflammation in the liver, which, in turn, can lead to liver cancer. Several ...
2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
PhIP has been shown to induce DNA adducts and mutations. These adducts have been found in a wide variety of sensitive tissues ... DNA and protein adducts were formed in the colon and blood. However, the adducts were unstable and declined over a 24-hour ... 1999). DNA and protein adduct formation in the colon and blood of humans after exposure to a dietary-relevant dose of 2-amino-1 ... PhIP has also formed DNA adducts in vivo in both rats and monkeys. PhIP has been tested for carcinogenicity in both mice and ...
Riddelliine
In rats gavaged with riddelliine, a set of DNA adducts of dehydroretronecine (DHS) in liver DNA can serve as biomarkers for the ... the resulting carbocation can bind to two DNA bases, producing another cross-linked DNA adduct. In both cases, the covalently ... To date, 8 DHP-derived DNA adducts have been observed, all of which contribute to the tumorigenicity of riddelliine. ... Two possible pathways emerge from this cytotoxic intermediate, both of which produce similar tumorigenic DNA adducts. Neither ...
Aristolochic acid
... which can form DNA-base adducts, thus giving aristolochic acid I its mutagenic properties. Aristolactam I adducts that are ... Nephropathy caused by aristolochic acid consumption is not mechanistically understood, but DNA adducts characteristic of ... "Exceptionally long-term persistence of DNA adducts formed by carcinogenic aristolochic acid I in renal tissue from patients ... have AAN can be confirmed through phytochemical analysis of plant products consumed and detection of aristolactam DNA adducts ...
Long-term effects of alcohol
Acetaldehyde can react with DNA to create DNA adducts including the Cr-Pdg adduct. This Cr-PdG adduct "is likely to play a ... Brooks P, Theruvathu J, Cho CH, Purohit V (2006). "Acetaldehyde-DNA Adducts: Implications for the Molecular Mechanism of ... owing to its multiple mutagenic effects on DNA." ...
M1G
M1dG is the major endogenous DNA adduct in humans. M1dG adducts have been detected in cell DNA in liver, leucocytes, pancreas ... of a specific type of DNA adduct called M1dG. The M1dG adduct in turn is formed by a condensation reaction between guanosine ... Detection and quantification of M1dG adducts in the body as measured by free M1G is a tool for detecting DNA damage that may ... "Metabolism in vitro and in vivo of the DNA base adduct, M1G". Chem. Res. Toxicol. 20 (3): 550-7. doi:10.1021/tx600334x. PMID ...
Anthracycline
... s can also form adducts with DNA by a single covalent bond through an aminal linkage from the 3'-amino of ... Cutts SM, Nudelman A, Rephaeli A, Phillips DR (February 2005). "The power and potential of doxorubicin-DNA adducts". IUBMB Life ... The supply of extracellular formaldehyde using formaldehyde-releasing prodrugs can promote covalent DNA adduct formation. Such ... Anthracyclines intercalated into DNA, form a stable anthracycline-DNA-topoisomerase II ternary complex thus "poisoning" the ...
DNA repair
"bulky adduct formation" (e.g., benzo[a]pyrene diol epoxide-dG adduct, aristolactam I-dA adduct) mismatch of bases, due to ... Reduced expression of DNA repair genes causes deficient DNA repair. When DNA repair is deficient DNA damages remain in cells at ... Biology portal Accelerated aging disease Aging DNA Cell cycle DNA damage (naturally occurring) DNA damage theory of aging DNA ... Human DNA Repair Genes 3D structures of some DNA repair enzymes Human DNA repair diseases DNA repair special interest group DNA ...
Aristolochia
Metabolites of aristolochic acid enter the cell nucleus and form adducts on DNA. While adducts on the transcribed DNA strand ... the adducts on the non-transcribed strand remain and eventually cause DNA replication errors. These adducts have a preference ... "Aristolactam I a metabolite of aristolochic acid I upon activation forms an adduct found in DNA of patients with Chinese herbs ... "Aristolactam I a metabolite of aristolochic acid I upon activation forms an adduct found in DNA of patients with Chinese herbs ...
Toxicodynamics
These diol-epoxides covalently bind with DNA base pairs, most often with guanine and adenine to form stable adducts within the ... One mechanism of action for genotoxic carcinogens includes the formation of DNA adducts. Once the PAH compound enters an ... A biological target, also known as the site of action, can be binding proteins, ion channels, DNA, or a variety of other ... Since these toxicants do not directly act on DNA, little is known about the mechanistic pathway. It has been proposed that ...
DNA damage (naturally occurring)
Ageing Aging brain AP site Direct DNA damage DNA DNA adduct DNA damage theory of aging DNA repair DNA replication Free radical ... estimated that there were 24,000 steady state oxidative DNA adducts per cell in young rats and 66,000 adducts per cell in old ... DNA damage is an alteration in the chemical structure of DNA, such as a break in a strand of DNA, a nucleobase missing from the ... DNA damage is an abnormal chemical structure in DNA, while a mutation is a change in the sequence of base pairs. DNA damages ...
Oxoguanine glycosylase
"Tracing the fates of site-specifically introduced DNA adducts in the human genome". DNA Repair. 15: 11-20. doi:10.1016/j.dnarep ... Park J, Chen L, Tockman MS, Elahi A, Lazarus P (February 2004). "The human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) DNA repair ... "Role of XRCC1 in the coordination and stimulation of oxidative DNA damage repair initiated by the DNA glycosylase hOGG1". The ... Gao T, Joyce BT, Liu L, Zheng Y, Dai Q, Zhang Z, Zhang W, Shrubsole MJ, Tao MH, Schwartz J, Baccarelli A, Hou L (2016). "DNA ...
Chlormadinone acetate
In principle, DNA adduct formation is not unique for CPA. DNA adducts in the rat liver were also found after in vitro ... Werner S, Kunz S, Beckurts T, Heidecke CD, Wolff T, Schwarz LR (December 1997). "Formation of DNA adducts by cyproterone ... 8-11] However, the adduct level generated by chlormadinone and megestrol is about 30 to 50 times lower than that after CPA.[12 ... Martelli A, Mattioli F, Ghia M, Mereto E, Brambilla G (May 1996). "Comparative study of DNA repair induced by cyproterone ...
Senescence
These adducts can further rearrange to form reactive species, which can then cross-link the structural proteins or DNA to ... Horvath S (2013). "DNA methylation age of human tissues and cell types". Genome Biology. 14 (10): R115. doi:10.1186/gb-2013-14- ... can react with certain amino acids such as lysine and arginine and certain DNA bases such as guanine to produce sugar adducts, ... Pan MR, Li K, Lin SY, Hung WC (May 2016). "Connecting the Dots: From DNA Damage and Repair to Aging". International Journal of ...
Aflatoxin B1
These adducts and alterations represent lesions which, upon DNA replication cause the insertion of a mis-matched base in the ... This active form then intercalates between DNA base residues and forms adducts with guanine residues, most commonly aflatoxin ... human liver cells with aflatoxin B1 at doses that ranged from 3-5 μmol/L resulted in the formation of aflatoxin B1-DNA adducts ... These adducts may then rearrange or become removed from the backbone all-together, forming an apurinic site. ...
Melamine cyanurate
The substance is best described as a melamine-cyanuric acid complex, or non-covalent adduct. The two compounds do not form a ... reminiscent of the guanine-cytosine base pairs found in DNA. Melamine cyanurate forms spoke-like crystals from aqueous ... Melamine cyanurate, also known as melamine-cyanuric acid adduct or melamine-cyanuric acid complex, is a crystalline complex ...
Enzyme inhibitor
This is a potent enzyme inhibitor, in this case preventing the RNA polymerase II enzyme from transcribing DNA. The algal toxin ... These electrophilic groups react with amino acid side chains to form covalent adducts. The residues modified are those with ... Satz AL, Kuai L, Peng X (May 2021). "Selections and screenings of DNA-encoded chemical libraries against enzyme and cellular ... Inglese J, Blatchly RA, Benkovic SJ (May 1989). "A multisubstrate adduct inhibitor of a purine biosynthetic enzyme with a ...
DNA damage theory of aging
DNA-protein crosslinks and malondialdehyde adducts (reviewed in Bernstein et al.). Increasing DNA damage with age has been ... DNA polymerase gamma is the enzyme that replicates mitochondrial DNA. A mouse mutant with a defect in this DNA polymerase is ... If a DNA repair protein is deficient, unrepaired DNA damages tend to accumulate. Such accumulated DNA damages appear to cause ... DNA damages and mutations are related because DNA damages often cause errors of DNA synthesis during replication or repair and ...
Roger Y. Tsien
Illumina integrated this concept with DNA cloning for their next generation sequencer. Tsien was a pioneer of calcium imaging ... "FLASH-EDT2": Fluorescein arsenical helix binder, bis-EDT adduct, "EDT": 1,2-ethanedithiol. Mouse experiments by Tsien's group ... filed a patent of stepwise ("base-by-base") sequencing with removable 3' blockers on DNA arrays. ...
Aziridines
... which is mutagenic in a wide range of test systems and forms DNA adducts that are promutagenic. The features that are ... aziridines are subject to attack and ring-opening by endogenous nucleophiles such as nitrogenous bases in DNA base pairs, ...
Angelicin
This impedes DNA replication more prominently due to the inability for the two strands of DNA helix to separate. Both psoralen ... angelicin with unsaturated fatty acid chains such as linolenic acid in a manner similar to the formation of pyrimidine adducts ... DNA photobinding is the most studied aspect of the photobiology and photochemistry of angelicin. According to the mechanism, ... In most cases the 4,5'-dimethylangelicin is applied owing to its firm binding and specificity to DNA. Also, it was shown that ...
Malondialdehyde
... reacts with deoxyadenosine and deoxyguanosine in DNA, forming DNA adducts, the primary one being M1G, which is ... Marnett LJ (1999). "Lipid peroxidation-DNA damage by malondialdehyde". Mutat. Res. 424 (1-2): 83-95. doi:10.1016/S0027-5107(99) ... and is one of the many reactive electrophile species that cause toxic stress in cells and form covalent protein adducts ...
Cruciferous vegetables
"Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a ...
Psoralen
"Induction of direct repeat recombination by psoralen-DNA adducts in Saccharomyces cerevisiae: defects in DNA repair increase ... Psoralen intercalates into the DNA double helix where it is ideally positioned to form one or more adducts with adjacent ... the affinity of the psoralen for DNA is directly related to the concentration of the psoralen in the DNA chamber after ... Psoralen intercalates into DNA and on exposure to ultraviolet (UVA) radiation can form monoadducts and covalent interstrand ...
Stephen J. Lippard
... cross-link as the major adduct on platinated single-stranded DNA, identification of the major adduct on double-stranded DNA, ... The interaction of Cisplatin and DNA results in the formation of DNA-DNA interstrand and intrastrand crosslinks which block DNA ... Lippard and his students examined sequences of DNA and RNA and incorporated sulfur atoms into the sugar-phosphate backbone, ... Cohen, GL; Bauer, WR; Barton, JK; Lippard, SJ (9 March 1979). "Binding of cis- and trans-dichlorodiammineplatinum(II) to DNA: ...
Dillapiole
"32P-Post-labelling analysis of DNA adducts formed in the livers of animals treated with safrole, estragole and other naturally- ...
CHST14
Previously, this condition has been independently referred to as adducted thumb-clubfoot syndrome, Ehlers-Danlos syndrome, ... DNA Research. 12 (2): 117-26. doi:10.1093/dnares/12.2.117. PMID 16303743. Mikami T, Mizumoto S, Kago N, Kitagawa H, Sugahara K ... and adducted thumb clubfoot syndrome (ATCS) represent a single clinical entity caused by mutations in the dermatan-4- ... "Loss of dermatan-4-sulfotransferase 1 function results in adducted thumb-clubfoot syndrome". American Journal of Human Genetics ...
Antigen
An autoantigen is usually a self-protein or protein complex (and sometimes DNA or RNA) that is recognized by the immune system ... An immunogen is an antigen substance (or adduct) that is able to trigger a humoral (innate) or cell-mediated immune response. ... For human tumors without a viral etiology, novel peptides (neo-epitopes) are created by tumor-specific DNA alterations. A large ...
Benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide
... pyrene Diol Epoxide with DNA Base Pairs: Insight into the Formation of Adducts of (+)-BaP DE-2 with DNA". Journal of Physical ... dA Adduct of (+)-(7S,8R,9S,10R)-7,8-Dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in a fully Complementary DNA Duplex ... N6-deoxyadenosine adduct of (9S,10R)-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in a DNA duplex". Biochemistry. 42 (6): 1410- ... Benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide has been shown to bind to an N2 atom of a guanine nucleobase in DNA, distorting the ...
List of skin conditions
Adams-Oliver syndrome Adducted thumbs syndrome Albright's hereditary osteodystrophy Angelman syndrome Apert syndrome ( ... leishmaniasis Wheat warehouse itch Virus-related cutaneous conditions are caused by two main groups of viruses-DNA and RNA ...
Moor frog
Products of the breakdown of DNA are found in higher concentrations in frozen moor frogs suggesting that freezing is a highly ... At temperatures immediately below freezing frogs assume an overwintering posture with their limbs adducted. When touched at ... However, in the aforementioned Siberian and Danish populations mitochondrial DNA testing revealed that they were closely ...
Droloxifene
Unlike tamoxifen, droloxifene does not produce DNA adduct or liver tumors in animals. Afimoxifene (4-hydroxytamoxifen) ...
Monovalent cation:proton antiporter-2
ISBN 978-0-444-82442-4. Munro AW, Ritchie GY, Lamb AJ, Douglas RM, Booth IR (March 1991). "The cloning and DNA sequence of the ... 2010) found that reduced glutathione stabilizes an inter-domain association between two KTN folds, whereas large adducts ... and glutathione adducts that form during electrophile detoxification and activate Kef. Roosild et al. ( ...
Oxidative stress
There is also a steady state level of oxidative damages in the DNA of a cell. There are about 24,000 oxidative DNA adducts per ... Sperm DNA fragmentation appears to be an important factor in the aetiology of male infertility, since men with high DNA ... In rat urine, about 74,000 oxidative DNA adducts per cell are excreted daily. ... Most long-term effects are caused by damage to DNA. DNA damage induced by ionizing radiation is similar to oxidative stress, ...
Phenolic content in wine
Acutissimin A aesculetin Anthocyanidin-caftaric acid adducts Astilbin Astringin B type proanthocyanidin dimers B type ... and protection of DNA, proteins and lipids from oxidative damage pursuant to Article 13(1) of Regulation (EC) No 1924/20061". ... Antioxidant Activities and Inhibition of Oxidation of Human Low-Density Lipoprotein Cholesterol and DNA Strand Breakage". ...
Dimethyl sulfoxide
DMSO is used in polymerase chain reaction (PCR) to inhibit secondary structures in the DNA template or the DNA primers. It is ... Cramer, R. E.; Bopp, T. T. (1977). "Graphical display of the enthalpies of adduct formation for Lewis acids and bases". Journal ... DMSO in a PCR is applicable for supercoiled plasmids (to relax before amplification) or DNA templates with high GC-content (to ... "Guidelines for PCR Optimization with Phusion High-Fidelity DNA Polymerase". Sawai M, Takase K, Teraoka H, Tsukada K (1990). " ...
Chlorophyllin
... pyrene-DNA adduct formation and alters cytochrome P450 1A1 and 1B1 expression and EROD activity in normal human mammary ... elevating the expression of DNA repair proteins p53 and PARP) and mitochondrial dysfunction and may be used as a therapeutic ... "Natural compounds in the human diet and their ability to bind mutagens prevents DNA-mutagen intercalation". Journal of ... of lung cancer both in in vitro and in vivo models through activation of mitochondrial signaling cascades and drug-DNA ...
Apiole
"32P-Post-labelling analysis of DNA adducts formed in the livers of animals treated with safrole, estragole and other naturally- ...
NIOSHTIC-2 Publications Search - 20034003 - PAH-DNA adducts in a Chinese population: relationship to PAH exposure, smoking and...
... and to examine the potential effects of smoking and polymorphisms of responsive genes on DNA adduct formation induced by PAH ... The present study was conducted in a Chinese population to evaluate the usefulness and sensitivity of PAH-DNA adduct as a ... PAH-DNA adducts in a Chinese population: relationship to PAH exposure, smoking and polymorphisms of metabolic and DNA repair ... The study suggests that PAH-DNA adducts may serve as a reliable biomarker of PAH exposure in occupational settings but may not ...
IARC Publications Website - Exocyclic DNA Adducts in Mutagenesis and Carcinogenesis
You are here: Home / Book and Report Series / IARC Scientific Publications / Exocyclic DNA Adducts in Mutagenesis and ... Exocyclic DNA Adducts in Mutagenesis and Carcinogenesis. IARC Scientific Publication No. 150. Edited by Singer B, Bartsch H ... volume comprise a comprehensive treatise on the current state of the art and scientific information on exocyclic DNA adducts. ... The use of exocyclic adducts as biomarkers offers a promising tool in studies of cancer etiology and prevention, particularly ...
Detection of carcinogen-DNA adducts in exfoliated urothelial cells of cigarette smokers: association with smoking, hemoglobin...
Sufficient DNA to detect 1 carcinogen-DNA adduct/10(9) normal nucleotides was obtained from 40 of the 73 samples. DNA was ... These adducts were from 2 to 20 times higher in the smokers than the nonsmokers. Two carcinogen-DNA adducts were qualitatively ... Twelve different carcinogen-DNA adducts and a diagonal zone of radioactivity could be found, but no sample contained all ... Detection of carcinogen-DNA adducts in exfoliated urothelial cells of cigarette smokers: association with smoking, hemoglobin ...
32P-Postlabeling of a DNA adduct derived from 4,4'-methylenedianiline in the olfactory epithelium of rats exposed by inhalation...
... of MDI with DNA; and a 32P-postlabeling method was adapted to detect (ii) a DNA adduct formed by 4,4-methylenedianiline (MDA ... were analyzed for DNA adducts. A 32P-postlabeling method was used to detect (i) adducts formed by the reaction of the ... the arylamine-derived DNA adduct was detected at the very low levels of 5, 9 and 10 adduct-nucleotides per 1010 nucleotides for ... The adduct cochromatographed with the one formed in the liver of rats after oral gavage of MDA. The results are discussed in ...
Determination of Tobacco-Specific Nitrosamine Lung DNA and Hemoglobin Adducts
NMR Studies of the Exocyclic 1,N<sup>6</sup>-Ethenodeoxyadenosine Adduct (edA) opposite Thymidine in a DNA Duplex. Nonplanar...
NMR Studies of the Exocyclic 1,N6-Ethenodeoxyadenosine Adduct (edA) opposite Thymidine in a DNA Duplex. Nonplanar Alignment of ... NMR Studies of the Exocyclic 1,N6-Ethenodeoxyadenosine Adduct (edA) opposite Thymidine in a DNA Duplex. Nonplanar Alignment of ... NMR Studies of the Exocyclic 1,N6-Ethenodeoxyadenosine Adduct (edA) opposite Thymidine in a DNA Duplex. Nonplanar Alignment of ... title = "NMR Studies of the Exocyclic 1,N6-Ethenodeoxyadenosine Adduct (edA) opposite Thymidine in a DNA Duplex. Nonplanar ...
Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by...
HCA-DNA adduct formation was stimulated by addition of PUFA, although high PUFA concentrations partly reduced this stimulating ... HCA-DNA adduct formation was stimulated by addition of PUFA, although high PUFA concentrations partly reduced this stimulating ... HCA-DNA adduct formation was stimulated by addition of PUFA, although high PUFA concentrations partly reduced this stimulating ... HCA-DNA adduct formation was stimulated by addition of PUFA, although high PUFA concentrations partly reduced this stimulating ...
DNA adducts and lung cancer risk: A prospective study - Cancer Epidemiology Unit (CEU)
Leukocyte DNA adducts were analyzed blindly using 32P postlabeling technique. Adducts were associated with the subsequent risk ... Besides, the association of DNA adduct levels with O 3 indicates a possible role for photochemical smog in determining DNA ... DNA adducts were measured in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition ( ... Our prospective study suggests that leukocyte DNA adducts may predict lung cancer risk of never-smokers. ...
Details for: DNA adducts : › WHO HQ Library catalog
Suppressive effects of methyl methacrylate on the mutagenicity and DNA adduct formation induced by 1-nitropyrene and benzo[a...
MMA inhibits the formation of 1-NP- and B[a]P-DNA. adducts in a dose-dependent manner. The DNA adduct of 1-NP reduced by MMA ... MMA inhibits the formation of 1-NP- and B[a]P-DNA. adducts in a dose-dependent manner. The DNA adduct of 1-NP reduced by MMA ... MMA inhibits the formation of 1-NP- and B[a]P-DNA. adducts in a dose-dependent manner. The DNA adduct of 1-NP reduced by MMA ... MMA inhibits the formation of 1-NP- and B[a]P-DNA. adducts in a dose-dependent manner. The DNA adduct of 1-NP reduced by MMA ...
Modulation of benzo[a]pyrene diolepoxide-DNA adduct levels in human white blood cells by CYP1A1, GSTM1 and GSTT1 polymorphism ...
BPDE-DNA adducts were detected in 69 of 133 (52%) DNA samples with a 100-fold variation (range 0.2-44 adducts/10(8) nt) and a ... whereby adducts increased with cigarette dose and the duration of smoking. Higher levels of BPDE-DNA adducts in individuals ... 0.2 adducts/10(8) nt) and 69 of 74 subjects with GSTM1*0/*0 (93%) had detectable adducts (,0.2 adducts/10(8) nt), The ... Mutated CYP1A1*1/*2 increased the adduct level in non-smokers from the exposed group (1.4 versus 2.2 adducts/10(8) nt), but had ...
IARC Publications Website - Exocyclic DNA Adducts in Mutagenesis and Carcinogenesis
You are here: Home / Book and Report Series / IARC Scientific Publications / Exocyclic DNA Adducts in Mutagenesis and ... Exocyclic DNA Adducts in Mutagenesis and Carcinogenesis. IARC Scientific Publication No. 150. Edited by Singer B, Bartsch H ... volume comprise a comprehensive treatise on the current state of the art and scientific information on exocyclic DNA adducts. ... The use of exocyclic adducts as biomarkers offers a promising tool in studies of cancer etiology and prevention, particularly ...
Biblio | Page 22 | Linus Pauling Institute | Oregon State University
DNA Adducts. Siddens LK, Bunde KL, Harper TA, McQuistan TJ, Löhr CV, Bramer LM, Waters KM, Tilton SC, Krueger SK, Williams DE ... DNA adduction and expression of select genes in the Cyp1b1 knockout mouse.. Toxicol Appl Pharmacol. 287(2):149-160. ... DNA adduction and expression of select genes in the Cyp1b1 knockout mouse.. Toxicol Appl Pharmacol. 287(2):149-160. ... DNA adduction and expression of select genes in the Cyp1b1 knockout mouse.. Toxicol Appl Pharmacol. 287(2):149-160. ...
A new platinum anticancer drug forms a highly stereoselective adduct with duplex DNA - Department of Oncology
... and a 14-mer DNA duplex (see schematic representation). ... drug forms a highly stereoselective adduct with duplex DNA Chen ... A new platinum anticancer drug forms a highly stereoselective adduct with duplex DNA ... The Effect of Oxygen Levels on the Biological Response of DNA Damage Inhibitors ... and a 14-mer DNA duplex (see schematic representation). ...
Catechol estrogen conjugates and DNA adducts in the kidney of male Syrian golden hamsters treated with 4-hydroxyestradiol:...
Formation of depurinating adducts by reaction of catechol estrogen-3,4-quinones with DNA was proposed to be a tumor initiating ... Devanesan, P, Todorovic, R, Zhao, J, Gross, ML, Rogan, EG & Cavalieri, EL 2001, Catechol estrogen conjugates and DNA adducts ... Dive into the research topics of Catechol estrogen conjugates and DNA adducts in the kidney of male Syrian golden hamsters ... N2 - Formation of depurinating adducts by reaction of catechol estrogen-3,4-quinones with DNA was proposed to be a tumor ...
Polycyclic aromatic hydrocarbon-DNA adducts among rickshaw drivers in Dhaka City, Bangladesh<...
... to quantify immunologically the WBC PAH-DNA adducts. Rickshaw drivers had a significantly higher WBC PAH-DNA adducts level than ... to quantify immunologically the WBC PAH-DNA adducts. Rickshaw drivers had a significantly higher WBC PAH-DNA adducts level than ... to quantify immunologically the WBC PAH-DNA adducts. Rickshaw drivers had a significantly higher WBC PAH-DNA adducts level than ... to quantify immunologically the WBC PAH-DNA adducts. Rickshaw drivers had a significantly higher WBC PAH-DNA adducts level than ...
Registration Dossier - ECHA
Acetaldehyde is a DNA reactive compound that forms specific DNA adducts (Matsuda et al., 1998; Brooks and Theruvathu 2005; ... DNA/protein cross-links and DNA binding (EU RAR 2008). Studies have demonstrated that the observed DNA-DNA or DNA-protein links ... Wang, M. et al (2006). Identification of an acetaldehyde adduct in human liver DNA and quantitation as N2-ethyldeoxyguanosine. ... Stein, S. et al (2006). Genotoxicity of acetaldehyde- and crotonaldehyde-induced 1,N2-propanodeoxyguanosine DNA adducts in ...
IMSEAR at SEARO: Inhibition of azoxymethane-induced DNA adduct formation by Aloe arborescens var. natalensis.
Shimpo K, Chihara T, Beppu H, Ida C, Kaneko T, Hoshino M, Kuzuya H. Inhibition of azoxymethane-induced DNA adduct formation by ... Inhibition of azoxymethane-induced DNA adduct formation by Aloe arborescens var. natalensis. ... we studied the effects of ALOE and ALOIN on the formation of AOM-induced DNA adducts (O6-methylguanine; O6-MeG) in rats. Male ... The animals were sacrificed 6 hours after the second injection to analyze DNA adducts (O6-MeG) in the colorectum. Dietary ...
Mechanistic investigations of DNA reactive carcinogens at low dose, through analysis of DNA adducts, mutations and DNA repair.
Understanding the importance of low‐molecular weight (ethylene oxide‐ and propylene oxide‐induced) DNA adducts and mutations in ... Influence of DNA Repair on Nonlinear Dose-Responses for Mutation by: Gareth Jenkins, et al. Published: (2013) ... This thesis presents a non-linear dose-response for MNU with a strong biological mechanism of action involving DNA repair.. ... The principle adduct responsible for MNU mutagenesis is 0 6Methylguanine (06MeG) that miscodes during replication and becomes ...
Advances in Molecular Toxicology, Volume 6 - 1st Edition
Andrew KLIGERMAN | Research biologist | Ph.D. | United States Environmental Protection Agency | US EPA | Integrated Systems...
DNA adducts in rat lung, liver and peripheral blood lymphocytes produced by i.p. administration of benzo[a]pyrene metabolites ... toward supercoiled phiX174 RFI DNA were assessed using a DNA nicking assay. The induction of DNA damage by these compounds in ... DNA adducts produced in vivo in rat lung, liver and peripheral blood lymphocytes following the i.p. administration of several ... Several DNA adducts were observed in each tissue, with maximal levels occurring at approximately 7 days after treatment. Lung D ...
Breast Cancer Epidemiology and Risk Factors: Epidemiology, Reproductive Factors, Endogenous Sex Hormones and Risk of Breast...
I. Polycyclic aromatic hydrocarbon DNA adducts. Cancer Epidemiol Biomarkers Prev. 2002 Aug. 11(8):677-85. [QxMD MEDLINE Link]. ... 20] The later the age at first full-term pregnancy, the more likely that DNA mistakes have occurred that will be propagated ... Candidates include genes for carcinogen-metabolizing enzymes, steroid hormone-metabolizing enzymes, DNA repair genes, and ... the phase that allows for DNA repair. The longer the interval from menarche to first pregnancy, the greater the adverse effect ...
Aristolochic acid IVa forms DNA adducts in vitro but is non-genotoxic in vivo. | Arch Toxicol;95(8): 2839-2850, 2021 08. |...
... among which two dA and three dG adducts were detected in reactions of AA IVa with calf thymus DNA (CT DNA). However, no DNA ... Ácidos Aristolóquicos/toxicidade Adutos de DNA/efeitos dos fármacos Dano ao DNA/efeitos dos fármacos DNA/efeitos dos fármacos ... Aristolochic acid IVa forms DNA adducts in vitro but is non-genotoxic in vivo.. Wan, Jingjing; Chen, Ruixue; Yang, Zhou; Xi, ... The competitive reaction of AA I and AA IVa with CT DNA, with adducts levels varying with pH of reaction revealed that AA IVa ...
Mass spectrometry-based method development for metabolites and DNA adducts of bisphenol A in liver slices and human breast...
Dibenzo[a,l]pyrene induced DNA adduct formation in lung tissue in vivo | College of Agricultural Sciences
Dibenzo[a,l]pyrene induced DNA adduct formation in lung tissue in vivo | College of Agricultural Sciences
Effect of phytochemicals on phIP-DNA adduct formation in human HepG2 cells and hepatocytes - UEA Digital Repository
Modified DNA adduct formationBiomarkersCarcinogenesisCarcinogen-DNA adductDifference in adductHemoglobin adductsMass spectrometryMutationsExocyclicPolycyclicMutagenicNucleotidesGenesBiologicalProteinBiomarkerBPDERepair PathwayExposureMutagenesisCarcinogensReplicationVitroThymidineReactiveSynthesisLymphocytesDetectableHumanPolymeraseBulkyChemicalDeoxyguanosineCovalently bindLevelsLiverStrandMolecularCellsSignificantly higherDifferencesDoseDetectProteinsEnzymesReactionSmokersBindSubstantiallyVivoEncodesCigarette
Modified DNA adduct formation1
- To confirm the antimutagenicity of MMA against 1-NP and B[a]P, a 32 P-postlabelling method was used to determine whether MMA modified DNA adduct formation produced by both compounds in calf thymus DNA. (elsevier.com)
Biomarkers4
- 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)
- We conclude that GSH and Cys conjugates of the 4-OHE and the 4-OHE-N7Gua adducts can be utilized as biomarkers to detect estrogenic imbalance and potential susceptibility to tumor initiation. (nebraska.edu)
- Exposures in the past have been diagnosed using DNA adducts and urinary metabolites as biomarkers. (cdc.gov)
Carcinogenesis3
- Finally, similar effects for n-3 and n-6 fatty acids suggested that adduct formation may not be the crucial mechanism behind the differential effects of PUFA on colon carcinogenesis that have been described. (maastrichtuniversity.nl)
- The DNA adduct of 1-NP reduced by MMA was greater than that of B[a]P. Thus, we suggested that MMA was possibly acting as an inhibitor of chemical carcinogenesis. (elsevier.com)
- 2015. Cytochrome P450 1b1 in polycyclic aromatic hydrocarbon (PAH)-induced skin carcinogenesis: Tumorigenicity of individual PAHs and coal-tar extract, DNA adduction and expression of select genes in the Cyp1b1 knockout mouse. . (oregonstate.edu)
Carcinogen-DNA adduct2
- Sufficient DNA to detect 1 carcinogen-DNA adduct/10(9) normal nucleotides was obtained from 40 of the 73 samples. (aacrjournals.org)
- Two-dimensional proton NMR studies are reported on the complementary d(C-A-T-G-T-G- T-A-C)·d(G-T-A-C-eA-C-A-T-G) nonanucleotide duplex (designated ϵdA·dT 9-mer duplex) containing 1,N 6 ethenodeoxyadenosine (ϵdA), a carcinogen-DNA adduct, positioned opposite thymidine in the center of the helix. (elsevier.com)
Difference in adduct3
- 0.2 adducts/10(8) nt), The difference in adduct level between the CSTM1*0/*0 and GSTM1 active genotypes was highly significant (P (archives-ouvertes.fr)
- No significant difference in adduct level between the GSTT1*0/*0 and GSTT1 active genotypes was seen. (archives-ouvertes.fr)
- Additionally, a 3-fold difference in adduct burden was observed by paving task such that mean adduct levels were lowest among roller operators (7 adducts per 10(10) nucleotides) and highest among screedmen (23 adducts per 10(10) nucleotides). (cdc.gov)
Hemoglobin adducts2
- Detection of carcinogen-DNA adducts in exfoliated urothelial cells of cigarette smokers: association with smoking, hemoglobin adducts, and urinary mutagenicity. (aacrjournals.org)
- Adducts were correlated significantly with the levels of 4-aminobiphenyl hemoglobin adducts and number of cigarettes smoked. (aacrjournals.org)
Mass spectrometry5
- Evidence for the 4-OHE-1-N7Gua depurinating adducts was obtained by mass spectrometry. (nebraska.edu)
- AA IVa reacted with 2'-deoxyadenosine (dA) and 2'- deoxyguanosine (dG) to form three dA and five dG adducts as identified by high-resolution mass spectrometry , among which two dA and three dG adducts were detected in reactions of AA IVa with calf thymus DNA (CT DNA ). (bvsalud.org)
- The researchers used mass-spectrometry-based methods they had developed previously for a different study in which they evaluated oral DNA damage caused by alcohol consumption. (acs.org)
- The adducted tripeptide is purified by solid phase extraction, separated by ultra-high pressure liquid chromatography, and detected by isotope dilution tandem mass spectrometry. (cdc.gov)
- Sulfur mustard can bind to DNA at several locations, including but not limited to the N 7 and O 6 position of Gua, and the N 3 position of Ade, all of which can be measured via immunoassays or mass spectrometry. (cdc.gov)
Mutations4
- Mechanistic investigations of DNA reactive carcinogens at low dose, through analysis of DNA adducts, mutations and DNA repair. (swan.ac.uk)
- 1 The detection of smoking-specific DNA adducts and mutations in the p53 gene in the breast tissue of smokers supports the biological plausibility of a positive association between cigarette smoking and breast cancer. (bmj.com)
- Unlike catalyzing error-free bypass of 8-oxodGuo, DNA polymerase λ is responsible for a significant part of Fapy·dG-induced G → T mutations in human cells. (nih.gov)
- Daughter cells that inherit these wrong bases carry mutations from which the original DNA sequence is unrecoverable (except in the rare case of a back mutation , for example, through gene conversion ). (wikipedia.org)
Exocyclic3
- Presentations at an international conference which resulted in this volume comprise a comprehensive treatise on the current state of the art and scientific information on exocyclic DNA adducts. (iarc.fr)
- NMR Studies of the Exocyclic 1,N6-Ethenodeoxyadenosine Adduct (edA) opposite Thymidine in a DNA Duplex. (elsevier.com)
- Dive into the research topics of 'NMR Studies of the Exocyclic 1,N 6 -Ethenodeoxyadenosine Adduct (edA) opposite Thymidine in a DNA Duplex. (elsevier.com)
Polycyclic1
- Serological characterization of polycyclic aromatic hydrocarbon diolepoxide-DNA adducts using monoclonal antibodies. (semanticscholar.org)
Mutagenic3
- In addition, levels of the putative N-(deoxyguanosin-8-yl)-4-aminobiphenyl adduct and a measure of total adducts were correlated with the mutagenic activity of the individual's urine. (aacrjournals.org)
- Mutagenic potential of DNA adducts formed by diol-epoxides, triol-epoxides and the K-region epoxide of chrysene in mammalian cells. (semanticscholar.org)
- In late-model decades, knowledge concerning the mutagenic properties of spe- cific DNA adducts has advanced dramatically, thanks in adipose part to the use of DNA reagents containing limited DNA adducts during biological experiments. (omcrew.ru)
Nucleotides2
- In the olfactory epithelium, on the other hand, the arylamine-derived DNA adduct was detected at the very low levels of 5, 9 and 10 adduct-nucleotides per 1010 nucleotides for the three dose groups, respectively. (fraunhofer.de)
- RESULTS: Among paving workers during the work-season, DNA adducts increased during each day of the workweek such that mean adduct levels were lowest on Mondays (3 adducts per 10(10) nucleotides) and highest on Fridays (46 adducts per 10(10) nucleotides). (cdc.gov)
Genes6
- PAH-DNA adducts in a Chinese population: relationship to PAH exposure, smoking and polymorphisms of metabolic and DNA repair genes. (cdc.gov)
- The present study was conducted in a Chinese population to evaluate the usefulness and sensitivity of PAH-DNA adduct as a biomarker of PAH exposure, and to examine the potential effects of smoking and polymorphisms of responsive genes on DNA adduct formation induced by PAH exposure. (cdc.gov)
- The polymorphisms of genes examined failed to show significant effects on PAH-induced adduct formation except ERCC2 Lys751Gln genotypes. (cdc.gov)
- The modulation of benzo[a]pyrene diolepoxide (BPDE)DNA adduct levels by polymorphisms in the CYP1A1, GSTM1 and GSTT1 genes was assessed in leukocytes of Caucasian males. (archives-ouvertes.fr)
- Many genes that were initially shown to influence life span have turned out to be involved in DNA damage repair and protection. (wikipedia.org)
- This crucial step triggers RNA polymerase II release from promoter-proximal pausing and expression of DNA damage response genes. (cell.com)
Biological4
- These data suggest that noninvasive, biological monitoring techniques can be applied to the study of carcinogen-DNA adducts in humans at high risk for bladder cancer. (aacrjournals.org)
- This thesis presents a non-linear dose-response for MNU with a strong biological mechanism of action involving DNA repair. (swan.ac.uk)
- The structural and biological consequences of DPCs have not been fully elucidated due to the complexity of these adducts. (jbc.org)
- The most common site of DPC formation in DNA following treatment with bis-electrophiles such as nitrogen mustards and cisplatin is the N7 position of guanine, but the resulting conjugates are hydrolytically labile and thus are not suitable for structural and biological studies. (jbc.org)
Protein6
- Complementary DNA and protein sequences of ethanol-inducible rat and human cytochrome P-450s. (genome.jp)
- DNA-protein cross-links (DPCs) are bulky DNA lesions that form both endogenously and following exposure to bis-electrophiles such as common antitumor agents. (jbc.org)
- Estrogen Drives Cellular Transformation and Mutagenesis in Cells Expressing the Breast Cancer-Associated R438W DNA Polymerase Lambda Protein. (nih.gov)
- show the mechanism of this bispecificity in FoxN3, revealing that DNA conformation differences enable the same protein to bind both sites. (cell.com)
- As a result, a simple and high-throughput method has been developed and validated for the quantitation of sulfur mustard blood protein adducts in low volume blood specimens which should be readily adaptable for quantifying human exposures to other alkylating agents. (cdc.gov)
- HBV demonstrates the ability to integrate and bind to p53 protein in the host DNA and propagate hepatocyte vulnerability through carcinogenic aflatoxin B1 (AFB1) damage. (bvsalud.org)
Biomarker3
- The study suggests that PAH-DNA adducts may serve as a reliable biomarker of PAH exposure in occupational settings but may not be sensitive enough to be used in populations with environmental exposures to PAHs. (cdc.gov)
- Accordingly, the primary objective of this study was to use DNA adducts as a biomarker of biologically effective dose and determine whether DNA damage resulted from occupational exposure to asphalt among paving workers. (cdc.gov)
- Sulfur mustard binds to reactive cysteine residues, forming a stable sulfur-hydroxyethylthioethyl [S-HETE] adduct that can be used as a long-term biomarker of sulfur mustard exposure in humans. (cdc.gov)
BPDE1
- Higher levels of BPDE-DNA adducts in individuals with the combined CYP1A1(1/*2 or *2A/*2A)-GSTM1*0/*0 genotype suggest that these genotype combinations are at increased risk for contracting lung cancer when exposed to PAH. (archives-ouvertes.fr)
Repair Pathway1
- Derek then was a Howard Hughes Research Fellow in the laboratory of Nobel Laureate Dr. Paul Modrich, where his work established that mismatch repair was the principal repair pathway invoked by DNA damage induced by cytotoxic chemotherapies, including cisplatin and methylating agents (Duckett et al. (moffitt.org)
Exposure4
- We measured PAH-DNA adducts in white blood cells (WBCs) as a marker of environmental and occupational PAH exposure in 46 rickshaw drivers (who pedal commercial unshielded three-wheelers for passenger transport) and 48 non-rickshaw drivers (comparison group) in Dhaka city. (nyu.edu)
- Mechanistic Influences for Mutation Induction Curves after Exposure to DNA-Reactive Carcinogens by: Gareth Jenkins, et al. (swan.ac.uk)
- Comparison of DNA Adducts from Exposure to Complex Mixtures in Various Human Tissues and Experimental Systems. (epa.gov)
- Compared with people who don't vape, four of the five e-cigarette users showed increased DNA damage related to acrolein exposure. (acs.org)
Mutagenesis2
- Furthermore, evidence is provided that implicates methlyguanine methyltransferase (MGMT) in protecting DNA from MNU induced mutagenesis by repairing 0 6MeG at low doses, thereby creating the NOGEL. (swan.ac.uk)
- Living on the Edge: DNA Polymerase Lambda between Genome Stability and Mutagenesis. (nih.gov)
Carcinogens2
- Bacteria were used as sensitive indicators for DNA damage and mammalian liver extracts for metabolic conversion of carcinogens to their active metabolic forms. (europa.eu)
- Aristolochic acids (AAs) are a family of natural compounds with AA I and AA II being known carcinogens , whose bioactivation causes DNA adducts formation. (bvsalud.org)
Replication7
- During replication, DNA polymerases tolerate patches of ribonucleotides on the parental strands to different extents. (jbc.org)
- The replication of damaged DNA before cell division can lead to the incorporation of wrong bases opposite damaged ones. (wikipedia.org)
- mismatch of bases, due to errors in DNA replication , in which the wrong DNA base is stitched into place in a newly forming DNA strand, or a DNA base is skipped over or mistakenly inserted. (wikipedia.org)
- To study the mechanism of DNA replication termination, Deegan et al. (cell.com)
- If the cell does not repair the damage so that normal DNA replication can take place, cancer could result. (acs.org)
- DNA adducts are quickly repaired, or DNA synthesis is blocked to avoid further replication of the mutation. (cdc.gov)
- During this talk, I will tell two such stories: 1) Structural variations in the human genome originate from different mechanisms related to DNA repair, replication, and retro-transposition. (jcbose.ac.in)
Vitro3
- Although TiO2 nanoparticles have been shown to induce DNA damage (comet assay) and chromosome damage (micronucleus assay, MN) in vitro, no study has systematically assessed the influence of medium com. (researchgate.net)
- Aristolochic acid IVa forms DNA adducts in vitro but is non-genotoxic in vivo. (bvsalud.org)
- In brief, although it could form DNA adducts in vitro , AA IVa was non-genotoxic in vivo, which was attributed to its low reactivity and biotransformation into an easily excreted metabolite rather than bioactivation. (bvsalud.org)
Thymidine1
- It has now been found, surprisingly, that even a strong base the conjugate acid of which has a pKa of greater than 11.5, for example, of about 12, may be used under certain conditions to bring about substantially complete deprotection e.g. of β-cyanoethyl protective group while substantially avoiding formation of cyanoethyl adducts to nucleobases, in particular thymidine. (justia.com)
Reactive3
- Non-linear dose-response of DNA-reactive genotoxins: Recommendations for data analysis by: George Johnson, et al. (swan.ac.uk)
- Non-linear dose¨Cresponse of DNA-reactive genotoxins: Recommendations for data analysis. (swan.ac.uk)
- The competitive reaction of AA I and AA IVa with CT DNA , with adducts levels varying with pH of reaction revealed that AA IVa was significantly less reactive than AA I, probably by hydroxyl deprotonation of AA IVa, which was explained by theoretical calculations for reaction barriers, energy levels of the molecular orbits , and charges at the reaction sites. (bvsalud.org)
Synthesis2
- In HCA-7 cells, highly expressing isoform COX-2, we investigated the effects of PUFA on prostaglandin synthesis and DNA adduct formation by the HCA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). (maastrichtuniversity.nl)
- Here, we employed a 2′-fluoro isostere approach to synthesize an oligonucleotide containing an analog of this lesion ( N 7 -CH 3 2′-F dG) and examined its miscoding potential with four Y-family translesion synthesis DNA polymerases (pols): human pol (hpol) η, hpol κ, and hpol ι and Dpo4 from the archaeal thermophile Sulfolobus solfataricus . (jbc.org)
Lymphocytes1
- DNA strand breakage and DNA adducts in lymphocytes of oral cancer patients. (bvsalud.org)
Detectable2
- In the lung, neither isocyanate adducts nor the arylamine aducts were detectable. (fraunhofer.de)
- All heterozygotes (CYP1A1*1/*2) from subjects of GSTM1 active type did not have detectable adducts, Among the GSTM1-deficient individuals (n = 69), 42 with the CYP1A1*/*1 genotype showed a lower adduct level (median 1.3, range 0.2-4.1 adducts/10(8) nt) compared with 26 individuals with heterozygous mutated CYP1A1*/*2 genotypes (median 2.5, range 0.4-6.1 adducts/10(8) nt, P (archives-ouvertes.fr)
Human11
- Two carcinogen-DNA adducts were qualitatively very similar to adducts described earlier in a study of human bladder biopsies. (aacrjournals.org)
- We reported previously that purified human DNA pol η (hpol η) can incorporate both deoxyribonucleoside triphosphates (dNTPs) and ribonucleoside triphosphates (rNTPs) and can use both DNA and RNA as substrates. (jbc.org)
- The majority of human DNA polymerases have been reported to misinsert ribonucleotides into genomes. (jbc.org)
- However, only PrimPol, DNA polymerase α, telomerase, and the mitochondrial human DNA polymerase (hpol) γ have been shown to tolerate an entire RNA strand. (jbc.org)
- Structural basis for the binding and incorporation of nucleotide analogs with L-stereochemistry by human DNA polymerase λ. (nih.gov)
- Cytotoxicity of and DNA adduct formation by ellipticine in human U87MG glioblastoma cancer cells. (nel.edu)
- Martinkova E, Dontenwill M, Frei E, Stiborova M. Cytotoxicity of and DNA adduct formation by ellipticine in human U87MG glioblastoma cancer cells. (nel.edu)
- Comparison of DNA Adduct Levels in Human Placenta from Polychlorinated Biphenyl Exposed Women and Smokers in Which CYP 1A1 Levels Are Similarly Elevated. (epa.gov)
- [1] In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in tens of thousands of individual molecular lesions per cell per day. (wikipedia.org)
- INT6/EIF3E interacts with ATM and is required for proper execution of the DNA damage response in human cells. (ens-lyon.fr)
- Human DNA Polymerase η Is Pre-Aligned. (neb.com)
Polymerase9
- Classical DNA and RNA polymerase (pol) enzymes have defined roles with their respective substrates, but several pols have been found to have multiple functions. (jbc.org)
- This gene encodes a DNA polymerase. (nih.gov)
- This particular polymerase, which is a member of the X family of DNA polymerases, likely plays a role in non-homologous end joining and other DNA repair processes. (nih.gov)
- A fidelity mechanism in DNA polymerase lambda promotes error-free bypass of 8-oxo-dG. (nih.gov)
- DNA polymerase ζ is a major determina. (neb.com)
- DNA polymerase eta is targeted by Mdm. (neb.com)
- DNA polymerase eta participates in th. (neb.com)
- DNA polymerase eta and chemotherapeut. (neb.com)
- Coordinating DNA polymerase traffic d. (neb.com)
Bulky1
- These modifications can in turn disrupt the molecules' regular helical structure by introducing non-native chemical bonds or bulky adducts that do not fit in the standard double helix. (wikipedia.org)
Chemical1
- The products of chemical reactions that result in the addition of extraneous chemical groups to DNA . (bvsalud.org)
Deoxyguanosine1
- Aside from abasic sites and ribonucleotides, the DNA adduct N 7 -methyl deoxyguanosine ( N 7 -CH 3 dG) is one of the most abundant lesions in mammalian DNA. (jbc.org)
Covalently bind1
- The quinones formed can be detoxified by reaction with glutathione (GSH) or can covalently bind to DNA. (nebraska.edu)
Levels5
- Tissues obtained from female Wistarrats exposed to a 0.9 µm aerosol of 4,4'-methylenediphenyl diisocyanate (MDI) for 17 h per day, 5 days per week, for one year at levels of 0, 0.3, 0.7 and 2.0 mg /m3, were analyzed for DNA adducts. (fraunhofer.de)
- Among rickshaw drivers, adduct levels tended to be positively associated with the duration of residence in the city and cigarette smoking. (nyu.edu)
- Adduct levels were not, however, higher among paving workers than among non-pavers. (cdc.gov)
- In contrast, levels of haemoglobin and DNA adducts decreased with increasing numbers of carbon atoms. (europa.eu)
- Dator and Balbo identified three DNA-damaging compounds, formaldehyde, acrolein and methylglyoxal, whose levels increased in the saliva after vaping. (acs.org)
Liver2
- The adduct cochromatographed with the one formed in the liver of rats after oral gavage of MDA. (fraunhofer.de)
- However, no DNA adducts were detected in the kidney , liver , and forestomach of orally dosed mice at 40 mg/kg/day for 2 days, and bone marrow micronucleus assay also yielded negative results . (bvsalud.org)
Strand2
- DNA polymerases catalyze DNA-template-directed extension of the 3'-end of a DNA strand. (nih.gov)
- When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including double-strand breaks and DNA crosslinkages (interstrand crosslinks or ICLs). (wikipedia.org)
Molecular2
- The 2015 Nobel Prize in Chemistry was awarded to Tomas Lindahl , Paul Modrich , and Aziz Sancar for their work on the molecular mechanisms of DNA repair processes. (wikipedia.org)
- DNA damage, due to environmental factors and normal metabolic processes inside the cell, occurs at a rate of 10,000 to 1,000,000 molecular lesions per cell per day. (wikipedia.org)
Cells6
- The presence of covalent modifications in DNA obtained from exfoliated urothelial cells of smokers and nonsmokers was determined using 32P postlabeling methods. (aacrjournals.org)
- Both IM and NS-398 inhibited adduct formation by HCA to nearly the same extent, indicating involvement of COX-2 rather than COX-1, while CYP1A2 activity in HCA-7 cells was demonstrated by addition of PEITC. (maastrichtuniversity.nl)
- Do Superoxide Dismutase and Catalase Protect Cells from DNA Damage Induced by Active Arsenicals? (researchgate.net)
- Mononuclear white blood cells were isolated and analyzed for DNA adducts via the (32)P-postlabeling assay and generalized linear models were used to evaluate the DNA adduct data. (cdc.gov)
- Today, researchers report that vaping may modify the genetic material, or DNA, in the oral cells of users, which could increase their cancer risk. (acs.org)
- To evaluate possible long-term effects of vaping, the team assessed DNA damage in the cells of the volunteers' mouths. (acs.org)
Significantly higher1
- Rickshaw drivers had a significantly higher WBC PAH-DNA adducts level than the non-rickshaw drivers. (nyu.edu)
Differences2
- Wiley K, Treadwell E, Manigaba K, Word B, Lyn-Cook B. Ethnic Differences in DNA Methyltransferases Expression in Patients with Systemic Lupus Erythematosus . (fda.gov)
- Using adducts as a measure of biologically effective dose, these findings (weekday trend and task-based differences) were consistent with a previous evaluation of absorbed dose in the same population. (cdc.gov)
Dose2
- adducts in a dose-dependent manner. (elsevier.com)
- Influence of DNA Repair on Nonlinear Dose-Responses for Mutation by: Gareth Jenkins, et al. (swan.ac.uk)
Detect1
- and a 32P-postlabeling method was adapted to detect (ii) a DNA adduct formed by 4,4'-methylenedianiline (MDA), a hydrolysis/decarboxylation product of MDI. (fraunhofer.de)
Proteins3
- Unlike proteins and RNA , DNA usually lacks tertiary structure and therefore damage or disturbance does not occur at that level. (wikipedia.org)
- DNA is, however, supercoiled and wound around "packaging" proteins called histones (in eukaryotes), and both superstructures are vulnerable to the effects of DNA damage. (wikipedia.org)
- Sulfur mustard is an alkylating agent which quickly reacts with nucleophiles such as DNA, RNA, water, lipids, peptides, and proteins via an episulfonium ion intermediate. (cdc.gov)
Enzymes2
- Additionally it is well recorded that ZEA modulates the procedure of cancerogenesis by influencing the procedure of apoptosis, ROS era, the actions of oxidative enzymes, DNA adduct development and fragmentation [8,9]. (cancerhugs.com)
- Dr. Duckett earned his PhD degree in Biochemistry from the University of Dundee under the mentorship of Professor David M. J. Lilley, a Member of Royal Society and the Director of the Cancer Research UK Nucleic Acid Structure Research Group, where Derek had a remarkable string of studies that defined the structures for DNA and RNA four-way helical junctions, and how these interact with resolving enzymes (Duckett, et al. (moffitt.org)
Reaction2
- Formation of depurinating adducts by reaction of catechol estrogen-3,4-quinones with DNA was proposed to be a tumor initiating event by estrogens [E.L. Cavalieri et al. (nebraska.edu)
- 1, N 6 -Ethenodeoxyadenosine (1, N 6 -ϵdA) is the major etheno lesion formed in the reaction of DNA with epoxides substituted with good leaving groups ( e.g. vinyl chloride epoxide). (jbc.org)
Smokers2
- These adducts were from 2 to 20 times higher in the smokers than the nonsmokers. (aacrjournals.org)
- They also want to see how the level of DNA adducts differs between e-cigarette users and regular cigarette smokers. (acs.org)
Bind2
Substantially1
- Smoking, age and gender did not substantially contribute to PAH-induced DNA adduct formation in this study. (cdc.gov)
Vivo2
- 2019) provide direct evidence that the bacterial-produced colibactin alkylates DNA in vivo , resulting in DNA adducts, which mediates its genotoxic effect. (cell.com)
- Surprisingly, replisome convergence is inherently inefficient but stimulated by the Pif1 and Rrm3 DNA helicases, which are also important during termination in vivo . (cell.com)
Encodes1
- [2] Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. (wikipedia.org)
Cigarette2
- At least four adducts appeared to be cigarette smoking related. (aacrjournals.org)
- Cigarette Smoke-Induced DNA Adducts in the Respiratory and Nonrespiratory Tissues of Rats. (epa.gov)