The tentative identification of DNA-adducts generated by trans-4-dimethylaminostilbene and trans-4-acetylaminostilbene in rats

Wildschutte, Michael; Franz, R.; Neumann, Hans‐Günter

doi:10.1016/0009-2797(90)90033-j

Cited by 4 publications

(1 citation statement)

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“…The association between bulky DNA-adduct formation and XRCC3 Thr/Met and Met/Met genotypes (particularly in the slow NAT-2 group) may be related to environmental exposure to genotoxic aromatic amines, such as trans-4-dimethylaminostilbene and 4-trans-acetylaminostilbene, 34 which are capable of forming DNA adducts to guanine and adenine and of inducing other secondary lesions of equal or greater importance, e.g., cross-links between bases. 4-Aminostilbene has been reported to induce high levels of chromosomal aberrations.…”

Section: Discussionmentioning

confidence: 99%

DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case-control study

et al. 2001

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Individuals differ widely in their ability to repair DNA damage, and DNA-repair deficiency may be involved in modulating cancer risk. In a case-control study of 124 bladder-cancer patients and 85 hospital controls (urological and non-urological), 3 DNA polymorphisms localized in 3 genes of different repair pathways (XRCC1-Arg399Gln, exon 10; XRCC3-Thr241Met, exon 7; XPD-Lys751Gln, exon 23) have been analyzed. Results were correlated with DNA damage measured as 32 P-post-labeling bulky DNA adducts in white blood cells from peripheral blood. Genotyping was performed by PCR-RFLP analysis, and allele frequencies in cases/controls were as follows: XRCC1-399Gln ‫؍‬ 0.34/0.39, XRCC3-241Met ‫؍‬ 0.48/0.35 and XPD-751Gln ‫؍‬ 0.42/0.42. Odds ratios (ORs) were significantly greater than 1 only for the XRCC3 (exon 7) variant, and they were consistent across the 2 control groups. XPD and XRCC1 appear to have no impact on the risk of bladder cancer. Indeed, the effect of XRCC3 was more evident in non-smokers [OR ‫؍‬ 4.8, 95% confidence interval (CI) 1.1-21.2]. XRCC3 apparently interacted with the N-acetyltransferase type 2 (NAT-2) genotype. The effect of XRCC3 was limited to the NAT-2 slow genotype (OR ‫؍‬ 3.4, 95% CI 1.5-7.9), suggesting that XRCC3 might be involved in a common repair pathway of bulky DNA adducts. In addition, the risk of having DNA adduct levels above the median was higher in NAT-2 slow acetylators, homozygotes for the XRCC3-241Met variant allele (OR ‫؍‬ 14.6, 95% CI 1.5-138). However, any discussion of interactions should be considered preliminary because of the small numbers involved. Our results suggest that bladder-cancer risk can be genetically modulated by XRCC3, which may repair DNA cross-link lesions produced by aromatic amines and other environmental chemicals. © 2001 Wiley-Liss, Inc. Key words: bladder cancer; XRCC1; XRCC3; XPD; DNA adductsA potentially important source of interindividual variability in response to carcinogens is DNA-repair capability. Apart from rare recessive inherited syndromes such as ataxia-telangiectasia, Fanconi's anemia and Bloom's syndrome, all of which are characterized by both chromosomal instability and high risk of cancer, and xeroderma pigmentosum, characterized by extreme susceptibility to UV-induced skin cancer, 1 individuals differ widely in the ability to repair DNA damage. 2 Polymorphisms in DNA-repair genes have been described. 3,4 Their role in modulating the risk of environmentally induced cancer is potentially important but has been studied only occasionally. In particular, XPD, XRCC1 and XRCC3 have been proposed as polymorphic genes that might be involved in environmental carcinogenesis. [5][6][7][8][9][10] The XRCC1 protein is involved in the base excision-repair pathway, 11 acting apparently as a scaffold protein, facilitating the repair reaction by binding DNA ligase III at its carboxy and DNA polymerase ␤ to its amino terminus. 12 XRCC3 participates in DNA double-strand breaks/recombinational repair and belongs to an emerging family of Rad51-related prot...

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Section: Discussionmentioning

confidence: 99%