CYTOCHROME-P-450 AND PEROXIDASE OXIDIZE DETOXICATION PRODUCTS OF CARCINOGENIC ARISTOLOCHIC ACIDS (ARISTOLACTAMS) TO REACTIVE METABOLITES BINDING TO DNA IN-VITRO

We report the analysis of DNA adducts formed from aristolactams I and II, which are the final metabolites derived from carcinogenic aristolo chic acids in vivo, after their oxidation by microsomal cytochrome P-4 50 and horseradish peroxidase in vitro. DNA adducts were detected and quantified using the nuclease Pl-enhanced variation of the P-32-postla beling assay. Quantitative analysis revelead that the extent of modifi cation of DNA by aristolactams activated by peroxidase was more than o ne order of magnitude higher than for activation by microsomal cytochr ome P-450, Peroxidase catalyzes the formation of active oxygen in the presence of NADH, H2O2 and aristolactams. Aristolactams are also oxidi zed by mammalian peroxidase prostaglandin H synthase. The possible rol e of aristolactams in carcinogenesis induced by aristolochic acid is d iscussed.