The effects of hydrogen peroxide on DNA repair activities

Abstract Oxygen free radicals generated by H 2 O 2 are involved in the multistage carcinogenic process; mechanisms include carcinogen activation, oxidative DNA damage, and tumor promotion. In this study, we have evaluated another potential mechanism of H 2 O 2 in carcinogenesis—modulation of DNA repair activities. Preexposure of human peripheral mononuclear leukocytes to H 2 O 2 significantly inhibited DNA repair activities in response to damage induced by N -methyl- N′ -nitro- N -nitrosoguanidine, measured as unscheduled DNA synthesis. The responses to H 2 O 2 were compared in four healthy human subjects with two sample preparations on different days. Results from multivariate general linear models showed that H 2 O 2 significantly inhibited DNA repair in a dose-dependent manner after adjustment for between- and within-subject variabilities. There was an estimate of 5.0 units ( dpm 5 × 10 5 cells) decrease in induced unscheduled DNA synthesis per unit (μM) increase of H 2 O 2 treatment. Furthermore, there was substantial variability in DNA repair activities for the same individual sampled on different days regardless of H 2 O 2 dose level. Results from this study suggest that H 2 O 2 not only can induce DNA damage, but also have suppressive effects on DNA repair.