Enhancement by copper, zinc superoxide dismutase of DNA damage and mutagenicity with hydrogen peroxide.
Oxidative DNA damage caused by hydrogen peroxide was enhanced by copper, zinc superoxide dismutase (CuZnSOD) in a concentration-dependent manner, as reflected by the formation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and strand breaks. Hydroxyl radical scavengers such as sodium azide, mannitol and 5,5-dimethyl-1-pyrroline N-oxide (DMPO), a metal chelator, diethylenetriamine-pentaacetic acid, and catalase decreased strand breaks and 8-OH-dG formation in DNA. The deoxyribose assay showed that hydroxyl free radicals were generated in the reaction of CuZnSOD with H2O2. CuZnSOD also caused enhancement of mutation in the pUC18 lacZ' gene in the presence of H2O2 when measured as a loss of alpha-complementation. Based on these results, we interpret the effects of CuZnSOD on hydrogen peroxide induced DNA damage and mutation as due to reactive oxygen species, probably hydroxyl free radicals, formed predominantly by the reaction of hydrogen peroxide and free Cu2+ released from oxidatively damaged CuZnSOD.
Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu, Korea.
R H
RH
Kim
S M
SM
Lee
J W
JW
Park
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002384:Catalysis; D002417:Cattle; D003300:Copper / Q000378:metabolism; D004249:DNA Damage; D004269:DNA, Bacterial / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D004926:Escherichia coli / Q000235:genetics; D005609:Free Radicals / Q000633:toxicity; D006861:Hydrogen Peroxide / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism*
D004269:DNA, Bacterial; D005609:Free Radicals; D009153:Mutagens; D003300:Copper; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D003849:Deoxyguanosine