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, β‐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 H(2)O(2) 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.