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Identification and Mutagenicity of Metabolites of 1-Nitropyrene Formed by Rat Liver¹

Division of Chemical Carcinogenesis, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York, 10595

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 µg/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 µg/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.

¹ This study was supported by National Institute of Environmental Health Sciences Award ES-02477. Presented in part at the 75th Annual Meeting of the American Association for Cancer Research, St. Louis, Mo., April, 1982 (7). This is Paper 52 of the series, "A Study of Chemical Carcinogenesis."

² To whom requests for reprints should be addressed.

Received 11/18/82. Accepted 4/ 5/83.

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