Stonard M D, Greig J B
Chem Biol Interact. 1976 Dec;15(4):365-79. doi: 10.1016/0009-2797(76)90141-1.
Three hexachlorobiphenyl isomers, 2,2',4,4',5,5'-hexachlorobiphenyl (I), 2,2',3,3',4,4'-hexachlorobiphenyl (II) and 2,2',3,4,4',5'-hexachlorobiphenyl (III), have been administered to rats and the effects of these three compounds upon hepatic microsomal drug metabolism and upon hepatic porphyrins have been studied. Comparisons have been made with hexachlorobenzen and a commercial polychlorinated biphenyl mixture, Aroclor 1254. From measurements of activities of microsomal drug oxidations in vitro, the durations of pharmacological actions of certain drugs in vivo and spectral shifts associated with cytochrome P-450 it is shown that the three pure hexachlorobiphenyl isomers initially produce changes in hepatic microsomal activity which resemble those seen after treatment with phenobarbitone (PB). In contrast, following chronic feeding of the isomers, compounds II and III but not I produce a pattern of hepatic microsomal enzyme activity which shows some characteristics of the 3-methylcholanthene (3-MC) and some characteristics of the phenobarbitone classes of inducer. Also, compounds II and III, but not I, cause accumulation in the liver of porphyrins containing either seven or eight carboxyl groups. These two responses are similar to those observed following hexachlorobenzene treatment and suggest that a relationship may exist between the mixed pattern of enzyme induction and the onset of hepatic porphyrin accumulation.
三种六氯联苯异构体，即2,2',4,4',5,5'-六氯联苯（I）、2,2',3,3',4,4'-六氯联苯（II）和2,2',3,4,4',5'-六氯联苯（III）已被给予大鼠，并研究了这三种化合物对肝脏微粒体药物代谢及肝脏卟啉的影响。已将其与六氯苯和一种商业多氯联苯混合物Aroclor 1254进行了比较。通过体外测量微粒体药物氧化活性、某些药物在体内的药理作用持续时间以及与细胞色素P-450相关的光谱变化，结果表明，三种纯六氯联苯异构体最初引起的肝脏微粒体活性变化类似于用苯巴比妥（PB）处理后所观察到的变化。相比之下，在长期喂食这些异构体后，化合物II和III而非I产生了一种肝脏微粒体酶活性模式，该模式显示出一些3-甲基胆蒽（3-MC）类诱导剂的特征以及一些苯巴比妥类诱导剂的特征。此外，化合物II和III而非I会导致含有七个或八个羧基的卟啉在肝脏中蓄积。这两种反应与六氯苯处理后观察到的反应相似，表明酶诱导的混合模式与肝脏卟啉蓄积的发生之间可能存在关联。
