Metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) by liver microsomes and isolated rabbit cytochrome P450 isozymes.
Metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) by liver microsomes and isolated rabbit cytochrome P450 isozymes.
复制标题
肝微粒体和分离的兔细胞色素 P450 同工酶对 2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶 (PhIP) 的代谢。
DOI：
10.1093/carcin/11.6.941
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发表时间：
1990
期刊：
影响因子：
4.7
通讯作者：
Felton,JS
中科院分区：
文献类型：
--
作者：
Turteltaub,KW;Knize,MG;Buonarati,MH;McManus,ME;Veronese,ME;Mazrimas,JA;Felton,JS
The cytochrome P450-dependent metabolism of the hetero-cyclic amine mutagen 2-amino-l-methyl-6-phenylirnidazo [4,5-b]pyridine (PhIP) has been determined. We investigated thein vitrometabolism 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 toSalmonellaTA98, 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.
