THE EFFECTS OF HYDROGEN-PEROXIDE ON DNA-REPAIR ACTIVITIES

Oxygen free radicals generated by H2O2 are involved in the multistage carcinogenic process; mechanisms include carcinogen activation, oxidat ive DNA damage, and tumor promotion. In this study, we have evaluated another potential mechanism of H2O2 in carcinogenesis-modulation of DN A repair activities. Preexposure of human peripheral mononuclear leuko cytes to H2O2 significantly inhibited DNA repair activities in respons e to damage induced by N-methyl-N'-nitro-N-nitrosoguanidine, measured as unscheduled DNA synthesis. The responses to H2O2 were compared in f our healthy human subjects with two sample preparations on different d ays. Results from multivariate general linear models showed that H2O2 significantly inhibited DNA repair in a dose-dependent manner after ad justment for between- and within-subject variabilities. There was an e stimate of 5.0 units (dpm/5 X 10(5) cells) decrease in induced unsched uled DNA synthesis per unit (mu M) increase of H2O2 treatment. Further more, there was substantial variability in DNA repair activities for t he same individual sampled on different days regardless of H2O2 dose l evel. Results from this study suggest that H2O2 not only can induce DN A damage, but also have suppressive effects on DNA repair.