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 P-32-5'-end-labeled DNA fragments. The DAB metabol ite N-hydroxy-4-aminoazobenzene (N-OH-AAB) was found to cause Cu(II)-mediat ed DNA damage, including 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) form ation, When an endogenous reductant, beta -nicotinamide adenine dinucleotid e (NADH) was added, the DNA damage was greatly enhanced. Very low concentra tions of N-OH-AAB could induce DNA damage via redox reactions. Catalase and a Cu(I)-specific chelator inhibited the DNA damage, suggesting the involve ment of H2O2 and Cu(I). A typical . OH scavenger did not inhibit the DNA da mage, The main reactive species are probably DNA-copper-hydroperoxo complex es. We conclude that oxidative DNA damage may play an important role in the carcinogenic processes of DAB, in addition to DNA adduct formation.