ENHANCEMENT BY COPPER, ZINC SUPEROXIDE-DISMUTASE OF DNA-DAMAGE AND MUTAGENICITY WITH HYDROGEN-PEROXIDE

Oxidative DNA damage caused by hydrogen peroxide was enhanced by coppe r, zinc superoxide dismutase (CuZnSOD) in a concentration-dependent ma nner, as reflected by the formation of 8-hydroxy-2'-deoxyguanosine (8- OH-dG) and strand breaks. Hydroxyl radical scavengers such as sodium a zide, mannitol and 5,5-dimethvl-1-pyrroline N-oxide (DMPO), a metal ch elator, diethylenetriamine- pentaacetic acid, and catalase decreased s trand breaks and 8-OH-dG formation in DNA. The deoxyribose assay showe d that hydroxyl free radicals were generated in the reaction of CuZnSO D with H2O2 CuZnSOD also caused enhancement of mutation in the pUC18 l acZ' gene in the presence of H2O2 when measured as a loss of alpha-com plementation. Based on these results, we interpret the effects of CuZn SOD on hydrogen peroxide induced DNA damage and mutation as due to rea ctive oxygen species, probably hydroxyl free radicals, formed predomin antly by the reaction of hydrogen peroxide and free Cu2+ released from oxidatively damaged CuZnSOD.