Identification and mutagenicity of metabolites of 1-nitropyrene formed by rat liver

The metabolism of 1-nitropyrene by rat liver 9000 X g supernatant was investigated. Under aerobic conditions, ring oxidation to 1-nitropyren-3-ol, 1-nitropyren-6-ol, 1-nitropyren-8-ol, and 4,5-dihydro-4,5-dihydroxy-1-nitropyrene and nitroreduction to 1-aminopyrene were observed. Metabolites were identified by their ultraviolet, mass, and nuclear magnetic resonance spectra; by chemical transformations; and by comparison to reference standards. When incubations were carried out in an atmosphere of 4% O2 in N2, 1-aminopyrene was the major metabolite. The mutagenic activities of 1-nitropyren-3-ol, 1-nitropyren-6-ol, and 1-nitrosopyrene were assessed in Salmonella typhimurium strains TA 98 and TA 100. In strain TA 98, without activation, doses of 0.5 micrograms/plate or less of these three compounds were more mutagenic than was 1-nitropyrene; however, their activities decreased rapidly at higher doses. In the presence of rat liver 9000 X g supernatant, they were less mutagenic than was 1-nitropyrene at all doses tested. In S. typhimurium TA 100, without activation, 1-nitropyren-3-ol, 1-nitropyren-6-ol, and 1-nitrosopyrene were more mutagenic than was 1-nitropyrene at doses of 0.25 micrograms/plate or less, but their activities decreased at higher doses. In strain TA 100, with activation, only 1-nitropyren-6-ol was more mutagenic than was 1-nitropyrene. The results of this study indicate that both nitroreduction and ring oxidation may be involved in the mutagenic activity of 1-nitropyrene.