Microsomal metabolism of 1-nitrobenzoOJpyrene to a highly mutagenic K-region dihydrodiol

Aerobic metabolism of l-nitrobenzo[e]pyrene (1-nitro-BeP) by rat liver mkrosomes produced 1-nitro-BeP trans-4,5-di-hydrodiol, 6-hydroxy-l-nitro-BeP, and 8-hydroxy-l-nitro-BeP. When 3,3,3-trichloropropylene 1,2-oxide was incorpor-ated into the metabolism, 1-nitro-BeP 4,5-oxide was the pre-dominant metabolite, and 1-nitro-BeP trans-4,5-dlhydrodio\ was not detected. All of the metabolites were purified by both reversed- and normal-phase HPLC and characterized by analysis of their mass and 500 MHz proton NMR spectral data. 1-Nitro-BeP was not metabolized under hypoxic con-ditions. 1-Nitro-BeP and its four metabolites were assayed in Salmonella typhimurium tester strains TA98, TA98NR and TA98/1,8-DNP6, both in the presence and absence of S9 activation. As predicted, 1-nitro-BeP was a weak mutagen without S9 (2 revertants//*g in TA98); the addition of S