Oxidative DNA damage induced by a metabolite of 2-naphthylamine, a smoking-related bladder carcinogen.
2-Naphthylamine (2-NA), a bladder carcinogen, is contained in cigarette smoke. DNA adduct formation is thought to be a major cause of DNA damage by carcinogenic aromatic amines. We have investigated whether a metabolite of 2-NA, 2-nitroso-1-naphthol (NO-naphthol) causes oxidative DNA damage, using (32)P-labeled DNA fragments. We compared the mechanism of DNA damage induced by NO-naphthol with that by N-hydroxy-4-aminobiphenyl (4-ABP(NHOH)), a metabolite of 4-aminobiphenyl, another smoking-related bladder carcinogen. NO-naphthol caused Cu(II)-mediated DNA damage at T > C > G residues, with non-enzymatic reduction by NADH. Catalase and bathocuproine, a Cu(I)-specific chelator, inhibited the DNA damage, suggesting the involvement of H(2)O(2) and Cu(I). Some free. OH scavengers also attenuated NO-naphthol-induced DNA damage, while free. OH scavengers had no effect on the DNA damage induced by 4-ABP(NHOH). This difference suggests that the reactive species formed by NO-naphthol has more free. OH-character than that by 4-ABP(NHOH). A high-pressure liquid chromatograph equipped with an electrochemical detector showed that NO-naphthol induced 8-oxo-7,8-dihydro-2'-deoxyguanosine formation in the presence of NADH and Cu(II). The oxidative DNA damage by these amino-aromatic compounds may participate in smoking-related bladder cancer, in addition to DNA adduct formation.
Ohnishi
Shiho
S
Department of Hygiene, Mie University School of Medicine, Tsu, Mie 514-8507, Japan.
Murata
Mariko
M
Kawanishi
Shosuke
S
D015081:2-Naphthylamine / Q000494:pharmacology*; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000611:Aminobiphenyl Compounds; D000818:Animals; D002273:Carcinogens; D002374:Catalase / Q000494:pharmacology; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D018736:DNA Adducts; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008956:Models, Chemical; D009603:Nitroso Compounds; D010100:Oxygen / Q000378:metabolism*; D010618:Phenanthrolines / Q000494:pharmacology; D012907:Smoking / Q000009:adverse effects*; D013950:Thymus Gland / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced*
D000611:Aminobiphenyl Compounds; D002273:Carcinogens; D018736:DNA Adducts; D009603:Nitroso Compounds; D010618:Phenanthrolines; C014593:N-hydroxy-4-aminobiphenyl; D003300:Copper; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; C002478:bathocuproine; D006861:Hydrogen Peroxide; C476511:2-nitroso-1-naphthol; D015081:2-Naphthylamine; D002374:Catalase; D003849:Deoxyguanosine; D010100:Oxygen