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METABOLISM OF 1-NITROPYRENE BY HUMAN, RAT, AND MOUSE INTESTINAL FLORA: NYTAGENICITY OF ISOLATED METABOLITES BY DIRECT ANALYSIS OF HPLC FRACTIONS WITH A MICROSUSPENSION REVERSE MUTATION ASSAY
Citation:
King, L., M. Kohan, S. George, J. Lewtas, AND L. Claxton. METABOLISM OF 1-NITROPYRENE BY HUMAN, RAT, AND MOUSE INTESTINAL FLORA: NYTAGENICITY OF ISOLATED METABOLITES BY DIRECT ANALYSIS OF HPLC FRACTIONS WITH A MICROSUSPENSION REVERSE MUTATION ASSAY. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-90/423 (NTIS PB91171785).
Description:
Among the nitro-substituted polycyclic aromatic hydrocarbons identified in environmental samples and known to be genotoxic, 1-nitropyrene is one of the most abundant. he biotransformation of 1-nitro[14C]pyrene by human, rat, and mouse intestinal microflora and the mutagenicity of the isolated metabolites by direct analysis of the HPLC fractions with a microsuspension mutation assay were investigated. -nitro[14C]pyrene was metabolized by human, rat and mouSe intestinal microflora to the following reductive metabolites; 1-aminopyrene, N-acetylaminopyrene, N-formyl-1-aminopyrene and two unknown metabolites identified as A and B. he predominant metabolite of 1-nitro[14C]pyrene produced by human, rat or mouse intestinal microflora following a 12 h incubation was 1-aminopyrene which accounted for 79 to 93% of the total 14C respectively. Only minor amounts of N-formyl-1-aminopyrene (1%), N-acetylaminopyrene (3 - 4%) were produced. The similarity in the distribution of the reductive metabolites suggests that a similar mechanism exists in the biotransformation of 1-nitropyrene by intestinal microflora of different mammalian species. irect mutagenicity analysis of the HPLC fractionS with the microsuspension mutation assay indicated that mutagenic fractions can be isolated and characterized using this methodology.