Oxidative DNA damage induced by an N-hydroxy metabolite of carcinogenic 4-dimethylaminoazobenzene.
Formation of adducts has been considered to be a major causal factor of DNA damage by carcinogenic aminoazo dyes. We investigated whether a metabolite of hepatocarcinogenic 4-dimethylaminoazobenzene (DAB) can cause oxidative DNA damage or not, using (32)P-5'-end-labeled DNA fragments. The DAB metabolite N-hydroxy-4-aminoazobenzene (N-OH-AAB) was found to cause Cu(II)-mediated DNA damage, including 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation. When an endogenous reductant, beta-nicotinamide adenine dinucleotide (NADH) was added, the DNA damage was greatly enhanced. Very low concentrations of N-OH-AAB could induce DNA damage via redox reactions. Catalase and a Cu(I)-specific chelator inhibited the DNA damage, suggesting the involvement of H2O2 and Cu(I). A typical.OH scavenger did not inhibit the DNA damage. The main reactive species are probably DNA-copper-hydroperoxo complexes. We conclude that oxidative DNA damage may play an important role in the carcinogenic processes of DAB, in addition to DNA adduct formation.
Ohnishi
S
S
Department of Hygiene, Mie University School of Medicine, Tsu, Mie 514-8507, Japan.
Murata
M
M
Degawa
M
M
Kawanishi
S
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D002273:Carcinogens / Q000737:chemistry*; D002374:Catalase; D003300:Copper / Q000633:toxicity; D018736:DNA Adducts / Q000737:chemistry*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry; D017665:Hydroxyl Radical / Q000737:chemistry*; D009243:NAD / Q000737:chemistry*; D010084:Oxidation-Reduction; D010128:p-Aminoazobenzene / Q000031:analogs & derivatives / Q000737:chemistry*; D004124:p-Dimethylaminoazobenzene / Q000737:chemistry*
D002273:Carcinogens; D018736:DNA Adducts; D009243:NAD; D017665:Hydroxyl Radical; D010128:p-Aminoazobenzene; C034529:N-hydroxy-4-aminoazobenzene; D003300:Copper; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004124:p-Dimethylaminoazobenzene; D006861:Hydrogen Peroxide; D002374:Catalase; D003849:Deoxyguanosine