Metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) by liver microsomes and isolated rabbit cytochrome P450 isozymes
| Autor: | J. A. Mazrimas, M. E. Veronese, Kenneth W. Turteltaub, M. H. Buonarati, James S. Felton, M. E. McManus, Mark G. Knize |
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| Rok vydání: | 1990 |
| Předmět: |
Male
Cancer Research Magnetic Resonance Spectroscopy Cytochrome Metabolite Isozyme Mice chemistry.chemical_compound Cytochrome P-450 Enzyme System Animals chemistry.chemical_classification 2-Amino-1-methyl-6-phenylimidazo(4 5-b)pyridine biology Imidazoles Cytochrome P450 General Medicine Metabolism Mice Inbred C57BL chemistry Biochemistry Heterocyclic amine Inactivation Metabolic Microsomes Liver biology.protein Microsome Methylcholanthrene Mutagens |
| Zdroj: | Carcinogenesis. 11:941-946 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/11.6.941 |
| Popis: | The cytochrome P450-dependent metabolism of the heterocyclic amine mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has been determined. We investigated the in vitro metabolism of PhIP by polycyclic hydrocarbon-induced mouse and rabbit liver microsomes, and by purified rabbit liver P450 isozymes. Following a 60 min incubation, 3-methylcholanthrene-induced mouse microsomes converted 36% of the PhIP to two major metabolites, N-hydroxy-PhIP and 4'-hydroxy-PhIP, with 43% total metabolism. Rabbit P450 form 6 and form 4 produced the same two major metabolites (20 and 5% total metabolism respectively). Additional metabolites were produced in low yields and amounts varied depending on the isozyme used (1-5%). Metabolites were not detected in incubations of PhIP with P450 forms 2 and 3C. N-Hydroxy-PhIP was found to be directly mutagenic to Salmonella TA98, while the 4'-hydroxy-PhIP was not mutagenic either with or without additional metabolic activation. These data suggest that the cytochrome P450IA isozymes are involved in the metabolism of PhIP by rabbit liver and that formation of N-hydroxy-PhIP is involved in the mutagenicity of PhIP. |
| Databáze: | OpenAIRE |
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