Metabolism of K-region derivatives of 1-nitropyrene by rat liver in vitro |
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Authors: | Roy Ajit K; El-Bayoumy Karam; Hecht Stephen S |
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Institution: | Section of Biological Chemistry, Division of Chemical Carcinogenesis, Naylor Dana Institute for Disease Prevention, American Health Foundation Valhalla, NY 10595, USA |
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Abstract: | The metabolism of K-region derivatives of 1-nitropyrene wasstudied in order to provide insight into factors that may contributeto their mutagenic activities and to obtain information on unknownmetabolites of 1-nitropyrene. Using 9000 g supernatant fromlivers of Aroclor-treated rats, 1-nitropyrene-4,5-diol, a mutagenicmetabolite of 1-nitropyrene, was metabolized to 1-aminopyrene-4,5-diol,a mixture of 1-nitropyrene-4,5,9,10-tetraols, 1-amino-4,5-pyrenedioneand 1-nitro-4,5-pyrenedione. 1-Nitro-5H-phenanthro4,5-bcd]pyran-5-one,a highly mutagenic lactone, was not detected. The metabolismof 1-nitro-4,5-pyrenedione yielded only 1-amino-4,5-pyrenedione;the lactone was not observed. No metabolites were detected whenthe lactone was incubated under conditions identical to thoseemployed for 1-nitro-4,5-diol and 1-nitro-4,5-pyrenedione. Uponre-examination of the metabolism of 1-nitropyrene, we were ableto detect 1-nitropyrene-4,5,9,10-tetraol, 1-amino-4,5-pyrenedioneand 1-nitro-4,5-pyrenedione as minor metabolites in additionto the major metabolites reported previously. The results ofthis study, combined with the mutagenicity data for the K-regionderivatives of 1-nitropyrene, suggest that nitroreduction of1-nitropyrene-4,5-diol and 1-nitro-4,5-pyrenedione to the correspondinghydroxylamines is an important pathway for their metabolic activationin Salmonella typhimurium and possibly in mammalian systems. |
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