Koga N, Kikuichi N, Kanamaru T, Kuroki H, Matsusue K, Ishida C, Ariyoshi N, Oguri K, Yoshimura H
Department of Food and Nutrition, Nakamura Gakuen University, Fukuoka, Japan.
Chemosphere. 1998 Oct-Nov;37(9-12):1895-904. doi: 10.1016/s0045-6535(98)00256-2.
The metabolism of 2,3',4',5-tetrachlorobiphenyl (TCB) was compared using liver microsomes and six isoforms of cytochrome P450 purified from rats, guinea pigs and hamsters. In microsomal study, the following species differences were observed: 1) Untreated guinea pigs and hamsters but not rats can metabolize this TCB to 3-hydroxy- or 4-hydroxy-2,3',4',5-TCB, 2) Guinea pig microsomes showed only 3-hydroxylating activity, whereas hamster microsomes showed higher activity of 4-hydroxylation than that of 3-hydroxylation. In common with three species, the 3-hydroxylation was accelerated by phenobarbital. The 4-hydroxylation in rats and hamsters was increased by pretreatment with 3-methylcholanthrene and 3,3',4,4',5-pentachlorobiphenyl. The hydroxylation activities of liver microsomes from the three species could be explained by an involvement of different isoforms of cytochrome P450. In addition, it is apparent that hamster CYP1A2 as well as hamster CYP2A8 is involved in the 4-hydroxylation of 2,3',4',5-TCB although it has no activity for 2,2',5,5'-TCB.
利用大鼠、豚鼠和仓鼠的肝脏微粒体以及纯化的六种细胞色素P450同工型，对2,3',4',5-四氯联苯（TCB）的代谢进行了比较。在微粒体研究中，观察到以下物种差异：1）未经处理的豚鼠和仓鼠而非大鼠能够将这种TCB代谢为3-羟基-或4-羟基-2,3',4',5-TCB；2）豚鼠微粒体仅表现出3-羟基化活性，而仓鼠微粒体表现出的4-羟基化活性高于3-羟基化活性。与三个物种相同的是，苯巴比妥可加速3-羟基化。大鼠和仓鼠经3-甲基胆蒽和3,3',4,4',5-五氯联苯预处理后，4-羟基化增加。三个物种肝脏微粒体的羟基化活性可用细胞色素P450不同同工型的参与来解释。此外，很明显仓鼠CYP1A2以及仓鼠CYP2A8参与了2,3',4',5-TCB的4-羟基化，尽管它对2,2',5,5'-TCB没有活性。
