A STUDY OF CHEMICAL CARCINOGENESIS .52. IDENTIFICATION AND MUTAGENICITY OF METABOLITES OF 1-NITROPYRENE FORMED BY RAT-LIVER

Abstract

The metabolism of [carcinogen] 1-nitropyrene by rat liver 9000 .times. g supernatant was investigated. Under aerobic conditions, ring oxidation to 1-nitropyren-3-ol, 1-nitropyreen-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 UV, mass and nuclear magnetic resonance spectra; by chemical transformations; and by comparison to reference standards. When incubations were carried out in an atmopshere 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 98, without activation, doses of 0.5 .mu.g/plate or less of these 3 compounds were more mutagenic than was 1-nitropyrene; however, their activities decreased rapidly at higher doses. In the presence of rat liver 9000 .times. 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 .mu.g/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. Both nitroreduction and ring oxidation may be involved in the mutagenic activity of 1-nitropyrene.