Carcinogenesb vol.15 no.3 pp.465-470, 1994 Activation of tran5-l,2-dihydro-l,2-dihydroxy-6-aminochrysene to genotoxic metabolites by rat and human cytochromes P450

• ̂ To whom reprint requests should be sent In order to address the hypothesis that 6-aminochrysene (6-AC) is converted to genotoxic products by cytochrome P450 enzymes via two activation pathways (iV-hydroxylation and epoxidation), the activation of 6-AC and trans-l*2-dihydro-l,2-dihydroxy-6-aminochrysene (6-AC-diol) to genotoxic metabolites was examined in rat and human liver microsomal cytochrome P450 enzymes using Salmonella typhimurium TA1535/pSK1002 and TA1535/pSK1002/pNM12 (NM2009) as tester strains. The latter bacteria, an O-acetyl-transferase-overexpressing strain, was highly sensitive to metabolites derived from activation of 6-AC, but not those from 6-AC-diol, using liver mkrosomes from phenobarbftal-treated rats or a reconstituted monooxygenase system contain-ing P4502B1 or-2B2, thus suggesting the roles of P450 an