Oxidative DNA damage by a metabolite of carcinogenic 1-nitropyrene.
Nitropyrenes are carcinogenic pollutants. Adduct formation following nitro-reduction is considered to be a major cause of nitropyrene-mediated DNA damage. We investigated the role of 1-nitrosopyrene, a metabolite of 1-nitropyrene, in causing oxidative DNA damage, using 32P-5'-end-labeled DNA. 1-Nitrosopyrene was found to facilitate Cu(II)-mediated DNA damage in the presence of NADH. Catalase and a Cu(I)-specific chelator attenuated DNA damage, indicating the involvement of H2O2 and Cu(I). Typical *OH scavenger did not have a significant effect. These results suggest that the main reactive species is probably a DNA-copper-hydroperoxo complex. We also measured 8-oxo-7,8-dihydro-2'-deoxyguanosine formation by 1-nitrosopyrene in the presence of Cu(II) and NADH, using an electrochemical detector coupled to a high-pressure liquid chromatograph. We conclude that oxidative DNA damage, in addition to DNA adduct formation, may play an important role in the carcinogenesis of nitropyrenes.
Ohnishi
S
S
Department of Hygiene, Mie University School of Medicine, 2-174, Edobashi, Tsu, Mie, 514-8507, Japan.
Murata
M
M
Fukuhara
K
K
Miyata
N
N
Kawanishi
S
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D002273:Carcinogens / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D004563:Electrochemistry / Q000379:methods; D016166:Free Radical Scavengers / Q000494:pharmacology; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007700:Kinetics; D009243:NAD / Q000737:chemistry; D010618:Phenanthrolines / Q000737:chemistry / Q000494:pharmacology; D011721:Pyrenes / Q000737:chemistry / Q000633:toxicity*
D002273:Carcinogens; D016166:Free Radical Scavengers; D010618:Phenanthrolines; D011721:Pyrenes; D009243:NAD; D003300:Copper; C044707:1-nitrosopyrene; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; C002478:bathocuproine; D006861:Hydrogen Peroxide; D003849:Deoxyguanosine; C032668:1-nitropyrene