title: Metal-mediated oxidative DNA damage induced by nitro-2-aminophenols.
abstract: Two hair dye components, carcinogenic 4-nitro-2-aminophenol and 5-nitro-2-aminophenol, induced Cu(II)-dependent DNA cleavage frequently at thymine and guanine residues in DNA fragments obtained from the c-Ha-ras-1 protooncogene. When the p53 tumor suppressor gene was used, 4-nitro-2-aminophenol caused Cu(II)-dependent piperidine-labile sites at poly G sequences. In the presence of Cu(II), both components increased 8-oxo-7,8-dihydro-2'-deoxyguanosine formation in DNA. The inhibitory effects of catalase and bathocuproine on DNA damage suggest the involvement of H2O2 and Cu(I). It is speculated that nitro-2-aminophenols undergo Cu(II)-mediated autoxidation to generate active oxygen species causing DNA damage which leads to their carcinogenesis.
authors.affiliation: Department of Hygiene, Mie University School of Medicine, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Oikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Hiraku
authors.forename: M
authors.initials: M
authors.lastname: Murata
authors.forename: N
authors.initials: N
authors.lastname: Yamashita
authors.forename: S
authors.initials: S
authors.lastname: Kawanishi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000814:Aniline Compounds / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D016158:Genes, p53; D011905:Genes, ras; D006202:Hair Dyes / Q000494:pharmacology; D006801:Humans; D009596:Nitrophenols / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*
chemical_list: D000814:Aniline Compounds; D006202:Hair Dyes; D009596:Nitrophenols; C087594:2-amino-5-nitrophenol; D003300:Copper; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D010100:Oxygen