Inductive Effect of Polychlorinated Biphenyls Mixture and Individual Isomers on the Hepatic Microsomal Enzymes
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概要
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The inductive effect of Kanechlor 400 (KC-400), the Japanese polychlorinated biphenyl (PCB) preparation containing 48% chlorine, and several individual PCB isomers on the hepatic microsomal enzymes of rats was investigated. Pretreatment with KC-400 increased significantly the activity of microsomal aminopyrine (AM) demethylase, aniline (AN) hydroxylase and NADPH-cytochrome c reductase, and the content of cytochromes P-450 and b_5 just like phenobarbital (PB)-pretreatment. However, it afforded the CO-difference spectrum revealing the peak at 448 nm same as pretreatment with 3-methylcholanthrene (MC). The inhibitory effect of SKF 525-A and 7,8-benzoflavone on AM demethylation and AN hydroxylation, respectively, in KC-400-induced microsomes also resembled that in microsomes induced by PB plus MC. Further studies using individual PCBs indicated that these compounds were divided into two groups ; namely, 4,4'-dichlorobiphenyl (DCB), 2,5,2', 5'-and 2,4,3', 4'-tetrachlorobiphenyl (TCB) were categorized as PB-type, whereas the other group including 3,4,3', 4'-TCB, 3,4,5,3', 4'-pentachlorobiphenyl (PenCB) and 3,4,5,3', 4', 5'-hexachlorobiphenyl (HCB) was categorized as MC-type inducers. Decachlorobiphenyl, the completely chlorinated biphenyl derivative, was found to belong to PB-type. These conclusions were further supported by a spectral study with hexobarbital, which induced type I spectral changes with microsomes from control and 2,4,3', 4'-TCB-treated rats, and caused modified type II spectral change with microsomes from 3,4,5,3', 4'-PenCB-treated rats. Considering these results with individual PCBs, it can be assumed that chlorination of both of the para-(4,4') and two of the meta-positions (3,3' or 5,5') of biphenyl is a minimum requirement for the structure to induce cytochrome P-448.
- 1978-04-25
著者
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佐伯 清太郎
Faculty of Pharmaceutical Sciences, Kyushu University
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吉村 英敏
九大 薬
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吉村 英敏
Faculty Of Pharmaceutical Sciences Kyushu University
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小沢 直記
Faculty Of Pharmaceutical Sciences Kyushu University
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佐伯 清太郎
Faculty Of Pharmaceutical Sciences Kyushu University
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