n-acetyl-1-aminopyrene and 1-aminopyrene

The comparative metabolism of 1-nitropyrene was studied in isolated rabbit, rat, and hamster tracheal epithelial cells commonly used in neoplastic transformation assays. The maximum total metabolite production for all species was attained at 2.0 x 10(6) cells and 4 hr incubation, with no significant increase after 20 hr. The majority of the metabolites produced by tracheal epithelial cells from each species were released into the surrounding medium. The metabolites retained by tracheal epithelial cells were qualitatively identical to those identified in the medium but were present at lower concentrations. The apparent Km for the metabolism of 1-nitropyrene by tracheal epithelial cells was in the order of rabbit (5.1 microM) < hamster (9.1 microM) < rat (13 microM). The apparent V/K value for the metabolism of 1-nitro-pyrene by tracheal epithelial cells was also in the order of rabbit (2.0 nmol/hr/mg protein) > hamster (1.6 nmol/hr/mg protein) > rat (0.48 nmol/hr/mg protein). Intrinsic clearance of the previously characterized mutagenic metabolites (3-OH-1-NAAP, K-DHD, 10-OH-1-NP, 1-AMP, and phenols 6- or 8-OH-1-NP) produced by tracheal epithelial cells at their approximate Km values also indicated that rabbit tracheal cells were more active in the production of these metabolites than either hamster or rat tracheal cells. Although the metabolism of 1-NP in isolated tracheal epithelial cells of these three species was qualitatively similar, rabbit tracheal cells are the most active in metabolizing 1-NP. These results are consistent with the possibility that tracheal epithelial cells may be a target tissue for NO2-PAHs carcinogenesis.

Topics: Animals; Biotransformation; Cell Count; Cells, Cultured; Cricetinae; Epithelial Cells; Epithelium; Kinetics; Oxidation-Reduction; Pyrenes; Rabbits; Rats; Species Specificity; Trachea

The metabolism of [14C]-1-nitropyrene by human, rat and mouse intestinal microflora and a bioassay-directed chemical analysis of the isolated metabolites by assaying HPLC fractions with a microsuspension reverse mutation assay were examined. [14C]-1-Nitropyrene was metabolized by human, rat, and mouse intestinal microflora to 1-aminopyrene, N-acetyl-1-aminopyrene, N-formyl-1-aminopyrene, and two unknown metabolites identified as A and B. The predominant metabolite produced by human, rat, or mouse intestinal microflora following a 12-h incubation with [14C]-1-nitropyrene was 1-aminopyrene, which accounted for 93, 79, and 88% of the total 14C, respectively. Only minor amounts of N-formyl-1-aminopyrene (1.4, 1.2, and 1.0%), N-acetyl-1-aminopyrene (4.4, 3.0, and 3.4%), unknown A (1.0, 1.2, and 1.0%), and unknown B (3.3, 5.0, and 1.2%) were detected. These data suggest that a similar mechanism exists in the biotransformation of 1-nitropyrene by intestinal microflora from all three sources. Direct mutagenicity analysis of the HPLC fractions produced by intestinal microflora with the microsuspension reverse mutation assay indicated that mutagenic fractions can be resolved using this methodology.

Topics: Animals; Bacteria; Biotransformation; Chromatography, High Pressure Liquid; Feces; Humans; Intestines; Male; Mice; Mutagenicity Tests; Mutagens; Pyrenes; Rats

The effect of 1-aminopyrene (1-AP) and N-acetylaminopyrene (1-NAAP) on rat hepatic microsomal monooxygenase system was investigated. Both drugs increased the total content of cytochrome P-450 (cyt. P-450). The substrate specificity and the electrophoretic pattern of 1-AP and 1-NAAP induced cytochrome(s) were compared with those of the major forms of cyt. P-450 induced by 3-methylcholanthrene (3-MC) and phenobarbital (PB). The results suggest that the form of cyt. P-450 induced by 1-AP and 1-NAAP resembles that one induced by 3-MC. Furthermore the abilities of liver microsomes from control or differently induced rats to ring hydroxylate and to activate 1-nitropyrene (1-NP) metabolites to species mutagenic for bacteria were compared. It was observed that: (1) 1-NAAP is a good substrate for microsome-mediated ring hydroxylation, whereas 1-AP is oxygenated only at a low extent; (2) 3-MC, 1-AP and 1-NAAP-stimulated microsomes are more active than control or PB-ones to ring hydroxylate 1-NAAP. As phenolic derivatives of 1-NAAP show high mutagenic activity, these results indicate that 1-AP and 1-NAAP induce toxification pathways of 1-NP in similar way, even if in less extent, as compared to 3-MC.

Topics: Animals; Biotransformation; Cytochrome P-450 Enzyme System; Electrophoresis, Polyacrylamide Gel; Enzyme Induction; In Vitro Techniques; Male; Microsomes, Liver; Mutagens; Pyrenes; Rats; Rats, Inbred Strains; Substrate Specificity