Metal-mediated oxidative DNA damage induced by nitro-2-aminophenols.
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.
Chen
F
F
Department of Hygiene, Mie University School of Medicine, Japan.
Oikawa
S
S
Hiraku
Y
Y
Murata
M
M
Yamashita
N
N
Kawanishi
S
S
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*
D000814:Aniline Compounds; D006202:Hair Dyes; D009596:Nitrophenols; C087594:2-amino-5-nitrophenol; D003300:Copper; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D010100:Oxygen