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  • exposure
  • 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)
  • 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)
  • ii) DHP-derived DNA adducts in blood can serve as a potential non-invasive biomarkers for assessing the exposure to riddelliine. (mdpi.com)
  • The HEI has supported research to develop sensitive and specific techniques for measuring polyaromatic hydrocarbon (PAH)-DNA adducts, a class of DNA adducts associated with exposure to constituents of diesel emissions and other combustion products. (epa.gov)
  • The third (18) , based on a sample of 19 subjects, found that in about 30% of cancer cases the DNA-adduct pattern that was detected resembled patterns that have been associated with smoking exposure. (aacrjournals.org)
  • These cell strains were used to monitor changes in gene expression and DNA adduct formation upon exposure to the pro-carcinogen BP in the presence or absence of chlorophyllin, a water soluble metalloporphyrin. (cdc.gov)
  • Therefore, AA-DNA adducts can not only be utilized as biomarkers for the assessment of AA exposure and markers of AA-induced UUC, but also be used for the mechanistic evaluation of its enzymatic activation and detoxification. (mdpi.com)
  • alcohol exposure, causing oxidative DNA damage (which is repairable), can result in epigenetic alterations at the sites of DNA repair. (wikipedia.org)
  • guanine
  • 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 main DNA adducts are N7-(2-carbamoyl-2-hydroxyethyl)-guanine (or N7-GA-Gua) and N3-(2-carbamoyl-2-hydroxyethyl)adenine (or N3-GA-Ade). (wikipedia.org)
  • PhIP's nitrenium ion intermediate is a powerful electrophile that has propensity to form C-8 guanine adducts with the DNA. (wikipedia.org)
  • O6-alkylguanine DNA alkyltransferase II (O6 AGT II) previously known as O6 Guanine transferase (ogt) is a bacterial protein that is involved in DNA repair together with Ada ( also known as O6 AGT I). Like AGT I, AGT II is responsible for the removal of alkyl groups from O6-alkyl guanine, O4-alkyl thymine and alkyl phosphotriester in the sugar-phosphate backbone of DNA. (wikipedia.org)
  • In humans, O6-alkylguanine DNA alkyltransferase preferentially removes alkyl groups from O6-alkyl guanine rather than from O6-alkyl thymine. (wikipedia.org)
  • rats
  • 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)
  • 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)
  • From 48 to 168 hours, the adduct levels in female rat blood were 4-fold greater than those in male rats. (mdpi.com)
  • In a dose response experiment, female rats were gavaged 0.1 and 1.0 mg/kg doses of riddelliine for three consecutive days and the DHPderived DNA adducts in blood DNA were assayed. (mdpi.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)
  • In addition, TAM-DNA adducts disappeared slowly over 21 days in rats on a control diet that were first given p.o. (aacrjournals.org)
  • Hemoglobin adducts are thought to be formed from the o-toluidine metabolite o-nitrosotoluene, which also causes urinary-bladder cancer in rats. (wikipedia.org)
  • genes
  • In another series of experiments, the researchers exposed genes to nitropyrene derivatives to determine if nitropyrene-DNA adducts stimulated homologous recombination. (epa.gov)
  • Among 7 NHMEC strains monitored using DNA-microarrays, up to 54 genes were induced upon treatment with BP alone, while 11 genes were downregulated. (cdc.gov)
  • DNA damage appears to be the primary underlying cause of cancer, and deficiencies in DNA repair genes likely underlie many forms of cancer. (wikipedia.org)
  • Reductions in expression of DNA repair genes (usually caused by epigenetic alterations such as promoter hypermethylation) are very common in cancers, and are ordinarily much more frequent than mutational defects in DNA repair genes in cancers. (wikipedia.org)
  • formation
  • 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)
  • Maximum DNA adduct formation occurred at 48 hr after treatment. (mdpi.com)
  • These data indicate that PAH-DNA adduct formation may influence breast cancer development, although the association does not appear to be dose dependent and may have a threshold effect. (aacrjournals.org)
  • A previous in vitro study showed that arsenic potentiated the formation of DNA adducts at low doses of BaP and arsenic. (cdc.gov)
  • These results demonstrate inter-individual variation in the bioactivation of BP and the potential of chlorophyllin for reducing the formation of BP-DNA lesions. (cdc.gov)
  • Although aristolochic acid I (AAI), the major component of the natural plant extract AA, might directly cause interstitial nephropathy, enzymatic activation of AAI to reactive intermediates capable of binding to DNA is a necessary step leading to the formation of AA-DNA adducts and subsequently AA-induced malignant transformation. (mdpi.com)
  • Weak carcinogenic activity has been shown, likely due to radical formation and induction of single-strand DNA breaks. (wikipedia.org)
  • liver
  • 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)
  • 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 adducts of TAM were measurable in rat liver 24 h after a single i.p. dose of 45 mg TAM/kg body weight and after daily p.o. dosing for 7 days with 5.0, 10.0, and 20.0 mg TAM/kg body weight. (aacrjournals.org)
  • For rat liver samples, the detection limit by CIA was 3 adducts per 10 9 nucleotides (0.2 fmol of adducts per 20 μg of DNA). (aacrjournals.org)
  • One general mechanism, increased DNA damage, is shared by some of the major causes of liver disease. (wikipedia.org)
  • In addition, activation of neutrophils in alcoholic liver disease contributes to the pathogenesis of hepatocellular damage by releasing reactive oxygen species (which can damage DNA). (wikipedia.org)
  • humans
  • ISBN missing] Evidence suggesting that this pathway is relevant to humans comes from numerous studies that detected o-toluidine hemoglobin adducts in humans (following both occupational and non-occupational exposures), consistent with observations in experimental animals. (wikipedia.org)
  • The human equivalent of AGT II is O6-alkylguanine DNA alkyltransferase, a protein that in humans is encoded by the O6-methylguanine DNA methyltransferase (MGMT) gene. (wikipedia.org)
  • calf thymus
  • Rabbits were immunized with calf thymus DNA, chemically modified with α-acetoxytamoxifen to 2.4 adducts per 100 nucleotides, and the resulting antisera were characterized by competitive dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) and chemiluminescence immunoassay (CIA). (aacrjournals.org)
  • covalent
  • Through a transesterification reaction, the catalytic tyrosine of the enzyme forms a transient phosphotyrosine covalent linkage, generating a nick in the DNA. (rupress.org)
  • lung
  • We hypothesized that arsenic co-treatment would significantly increase BaP adduct levels in C57BL/6 mouse target organs: skin and lung. (cdc.gov)
  • DNA was extracted from skin and lung and assayed by (32)P-postlabeling. (cdc.gov)
  • vitro
  • For assay validation, TAM-dG levels were determined by DELFIA, CIA, and 32 P-postlabeling in TAM-DNA samples modified in vitro to different levels, and comparable values were obtained in all three assays. (aacrjournals.org)
  • alkyltransferase
  • N7-methylguanine (N7mdG) and 06-methylguanine (O6mdG), and with the activity of the enzyme that repairs 06mdG adducts, 06- alkylguanine-DNA alkyltransferase (AGT). (cdc.gov)
  • carcinogenic
  • 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)
  • doses
  • In the rat experiments, TAM-DNA adduct levels determined by CIA compared well with those determined by 32 P-postlabeling, although the CIA gave an underestimation at the highest doses. (aacrjournals.org)
  • damage
  • DNA Damage, DNA Repair and Cancer, New Research Directions in DNA Repair, Prof. Clark Chen (Ed.), ISBN 978-953-51-1114-6, InTech, http://www.intechopen.com/books/new-research-directions-in-dna-repair/dna-damage-dna-repair-and-cancer Kastan MB (April 2008). (wikipedia.org)
  • R828112C046 How Do Chemicals in Diesel Engine Exhaust Damage DNA? (epa.gov)
  • To examine whether currently measurable PAH damage to DNA increases breast cancer risk, a population-based case-control study was undertaken on Long Island, NY. (aacrjournals.org)
  • ROS cause more than 20 types of DNA damage. (wikipedia.org)
  • If DNA repair is deficient, DNA damage tends to accumulate. (wikipedia.org)
  • Excess DNA damage may also increase epigenetic alterations due to errors during DNA repair. (wikipedia.org)
  • DNA Damage, DNA Repair and Cancer, New Research Directions in DNA Repair, Prof. Clark Chen (Ed.), ISBN 978-953-51-1114-6, InTech, http://www.intechopen.com/books/new-research-directions-in-dna-repair/dna-damage-dna-repair-and-cancer Harper JW, Elledge SJ (2007). (wikipedia.org)
  • Chlorophyllin
  • Following treatment of NHMEC strains (n=7) with BP (4 M) in the presence or absence of chlorophyllin (5 M), genome-wide -3fold changes in gene expression were monitored over 24h by DNA-microarrays. (cdc.gov)
  • A reduction in BPDE-DNA adduct levels (48% to 86%) was observed in cells exposed to chlorophyllin following treatment with BP plus chlorophyllin. (cdc.gov)
  • concentrations
  • 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)
  • BaP adduct levels in the skin of individual animals were positively related to skin arsenic concentrations. (cdc.gov)
  • tamoxifen
  • For the immunogen TAM-DNA, 50% inhibition was at 2.0 ± 0.11 (mean ± SE, n = 18) fmol of ( E )-α-( N 2 -deoxyguanosinyl)tamoxifen (TAM-dG) adduct in TAM-DNA by DELFIA. (aacrjournals.org)
  • The individual adducts TAM-dG and ( Z )-α-( N 2 -deoxyguanosinyl)tamoxifen and the individual compounds TAM and 4-OH-TAM gave DELFIA 50% inhibitions at 828, 2229, 5440, and 8250 fmol, respectively. (aacrjournals.org)
  • levels
  • There was no consistent elevation in risk with increasing adduct levels, nor was there a consistent association between adduct levels and two of the main sources of PAH, active or passive cigarette smoking or consumption of grilled and smoked foods. (aacrjournals.org)
  • protein
  • For example, protein-DNA adducts must be removed to allow repair by either nonhomologous end joining or homology-directed repair. (rupress.org)
  • Although originally the term related to adducts of DNA, the adductomic approach has now been adopted by protein chemists in their attempts to identify protein adducts. (wikipedia.org)
  • urine
  • Once in the bladder, N-hydroxy-o-toluidine can be released from the conjugates in an acidic urine environment to either react directly with DNA or be bio-activated via sulfation or acetylation by cytosolic sulfotransferases or N-acetyltransferases (presumably NAT1). (wikipedia.org)
  • Inhibition
  • For TAM-DNA modified to 4.8 adducts in 10 6 nucleotides, 50% inhibition was at 20.6 ± 6.6 (mean ± SE, n = 8) fmol of TAM-dG in TAM-DNA by DELFIA and at 0.92 ± 0.11 (mean ± SE, n = 10) fmol of TAM-dG in TAM-DNA by CIA. (aacrjournals.org)
  • No inhibition was observed in either assay with up to 20 μg (62.5 nmol of nucleotides) of unmodified DNA. (aacrjournals.org)
  • Inhibition of cellular proliferation and metastasis appears to be via induction of caspase-8, followed by caspase-3 and eventually DNA fragmentation. (wikipedia.org)
  • Cancer
  • In molecular genetics, a DNA adduct is a segment of DNA bound to a cancer-causing chemical. (wikipedia.org)
  • Effects independent of ER binding include breakage of single-stranded DNA, especially when interacting synergistically with nitric oxide in human breast cancer cells and the production of quinones and free radicals. (wikipedia.org)
  • When a DNA adduct forms at a site critical to the regulation of cell differentiation or growth it can cause cancer. (wikipedia.org)
  • strand
  • Repair of DNA double-strand breaks (DSBs) with complex ends poses a special challenge, as additional processing is required before DNA ligation. (rupress.org)
  • The decision to use NHEJ or HDR is governed in part by DNA resection, a nucleolytic process in which DSB ends are converted into 3′ single-strand DNA overhangs, an essential intermediate for the downstream steps of HDR and a potent inhibitor of NHEJ. (rupress.org)
  • After isomerization, the DNA phosphodiester backbone is restored when the 5′ OH of the broken DNA strand attacks the 3′ phosphotyrosine bond, liberating Top1 for subsequent cleavage and unwinding. (rupress.org)
  • the DNA can also be damaged by hydroxyl radicals produced during reoxidation of pentavalent chromium by hydrogen peroxide molecules present in the cell, which can cause double-strand breakage. (wikipedia.org)
  • form
  • Glycidamide also reacts with haemoglobine (Hb) to form a cysteine adduct, S-(20hydroxy-2carboxyethyl)cysteine. (wikipedia.org)
  • human
  • Relative efficiencies of the bacterial, yeast, and human DNA methyltransferases for the repair of O6-methylguanine and O4-methylthymine. (wikipedia.org)