Interindividual Variability in Response to Sodium Dichromate-Induced Oxidative DNA Damage: Role of the Ser326Cys Polymorphism in the DNA-Repair Protein of 8-Oxo-7,8-Dihydro-2'-Deoxyguanosine DNA Glycosylase 1

摘要: Although the genotoxic mechanism(s) of hexavalent chromium (CrVI) carcinogenicity remain to be fully elucidated, intracellular reduction CrVI and concomitant generation reactive intermediates including oxygen species subsequent oxidative damage DNA is believed contribute process carcinogenesis. In current study, substantial interindividual variation (7.19-25.84% 8.79-34.72% tail as assessed by conventional FPG-modified comet assay, respectively) in levels strand breaks after vitro treatment WBC with sodium dichromate (100 μmol/L, 1 hour) was shown within a group healthy adult volunteers ( n = 72) both formamidopyrimidine glycosylase–modified assays. No statistically significant correlation between glutathione S -transferases M1 or T1, NADPH quinone oxidoreductase (codon 187) X-ray repair cross complementation factor 194) genotypes individual were observed. However, individuals homozygous for Cys326 8-oxo 7,8-dihydro-2′-deoxyguanosine glycosylase (OGG1) polymorphism had elevation glycosylase–dependent when compared either Ser326/Ser326 Ser326/Cys326 P 0.008 0.003, respectively). contrast, no effect OGG1 genotype on background When divided basis genotype, Cys326/Cys326 < 0.05, one-way ANOVA followed Tukey test) higher ratio plasma antioxidant capacity than individuals. The results this study suggest that may represent phenotype deficient 8-oxo-7,8-dihydro-2′-deoxyguanosine, but only under conditions cellular stress. We hypothesize due oxidation residue. conclusion, biomarker susceptibility lung cancer risk are occupationally exposed CrVI.