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, oxidative DNA damage, and tumor promotion. In this study, we have evaluated another potential mechanism of H2O2 in carcinogenesis--modulation of DNA repair activities. Preexposure of human peripheral mononuclear leukocytes to H2O2 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 H2O2 were compared in four healthy human subjects with two sample preparations on different days. Results from multivariate general linear models showed that H2O2 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 x 10(5) cells) decrease in induced unscheduled DNA synthesis per unit (microM) increase of H2O2 treatment. Furthermore, there was substantial variability in DNA repair activities for the same individual sampled on different days regardless of H2O2 dose level. Results from this study suggest that H2O2 not only can induce DNA damage, but also have suppressive effects on DNA repair.
Hu
J J
JJ
Cancer Prevention Research Institute, New York, NY 10010.
Dubin
N
N
Kurland
D
D
Ma
B L
BL
Roush
G C
GC
D000328:Adult; D000704:Analysis of Variance; D004260:DNA Repair / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005609:Free Radicals; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D008875:Middle Aged; D015203:Reproducibility of Results; D013045:Species Specificity
D005609:Free Radicals; D008769:Methylnitronitrosoguanidine; D006861:Hydrogen Peroxide