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Title: Oxidative DNA damage induced by an N-hydroxy metabolite of carcinogenic 4-dimethylaminoazobenzene. Author: Ohnishi S, Murata M, Degawa M, Kawanishi S. Journal: Jpn J Cancer Res; 2001 Jan; 92(1):23-9. PubMed ID: 11173540. Abstract: 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.[Abstract] [Full Text] [Related] [New Search]