Haake J M, Merrill J C, Safe S
Can J Physiol Pharmacol. 1985 Sep;63(9):1096-100. doi: 10.1139/y85-180.
The metabolism of benzo[a]pyrene by halogenated biphenyl-induced rat hepatic microsomal monooxygenases was determined using a high pressure liquid chromatographic assay system. Incubation of benzo[a]pyrene with microsomes from rats pretreated with phenobarbitone or phenobarbitone-type inducers (2,2',4,4',5,5'-hexachlorobiphenyl, 2,2',4,4',6,6'-hexachlorobiphenyl, 2,2',5,5'-tetrachlorobiphenyl, 2,2',4,4',5,5'-hexabromobiphenyl, and 2,2',5,5'-tetrabromobiphenyl) resulted in increased overall metabolism of the hydrocarbon (less than fourfold) into phenolic, quinone, and diol metabolites, with the most striking increase observed in the formation of 4,5-dihydro-4,5-dihydroxybenzo[a]pyrene. In contrast, the metabolism of benzo[a]pyrene by microsomes from rats induced with 3-methylcholanthrene or 3,3',4,4'-tetrachlorobiphenyl resulted in a greater than 10-fold increase in overall benzo[a]pyrene metabolism, with the largest increases observed in the formation of the trans-7,8- and -9,10-dihydrodiol metabolites of benzo[a]pyrene. However, in comparison to control and phenobarbitone-induced microsomes, the oxidative conversion of benzo[a]pyrene by microsomes induced with 3-methylcholanthrene and 3,3',4,4'-tetrachlorobiphenyl into the 6,12-quinone was substantially inhibited. Previous reports have shown that the commercial halogenated biphenyl mixtures, fireMaster BP-6, and Aroclor 1254 are mixed-type inducers and that microsomes from rats pretreated with these mixtures markedly enhance the overall metabolism of benzo[a]pyrene. Not surprisingly, the metabolism of benzo[a]pyrene by microsomes from rats pretreated with the mixed-type inducers, 2,3,3',4,4'-penta-,2,3,3',4,4',5-hexa-, and 2',3,3',4,4',5-hexa- chlorobiphenyl was also increased and the metabolic profile was similar to that observed with fireMaster BP-6 and Aroclor 1254 induced microsomes.
使用高压液相色谱分析系统测定了卤代联苯诱导的大鼠肝微粒体单加氧酶对苯并[a]芘的代谢。将苯并[a]芘与用苯巴比妥或苯巴比妥类诱导剂（2,2',4,4',5,5'-六氯联苯、2,2',4,4',6,6'-六氯联苯、2,2',5,5'-四氯联苯、2,2',4,4',5,5'-六溴联苯和2,2',5,5'-四溴联苯）预处理的大鼠的微粒体一起温育，导致该烃类的总体代谢增加（不到四倍），生成酚类、醌类和二醇类代谢产物，其中在4,5-二氢-4,5-二羟基苯并[a]芘的形成中观察到最显著的增加。相比之下，用3-甲基胆蒽或3,3',4,4'-四氯联苯诱导的大鼠的微粒体对苯并[a]芘的代谢导致苯并[a]芘总体代谢增加超过10倍，其中在苯并[a]芘的反式-7,8-和-9,10-二氢二醇代谢产物的形成中观察到最大的增加。然而，与对照和苯巴比妥诱导的微粒体相比，用3-甲基胆蒽和3,3',4,4'-四氯联苯诱导的微粒体将苯并[a]芘氧化转化为6,12-醌的过程受到显著抑制。先前的报告表明，市售的卤代联苯混合物FireMaster BP-6和多氯联苯混合物Aroclor 1254是混合型诱导剂，用这些混合物预处理的大鼠的微粒体可显著增强苯并[a]芘的总体代谢。不出所料，用混合型诱导剂2,3,3',4,4'-五氯、2,3,3',4,4',5-六氯和2',3,3',4,4',5-六氯联苯预处理的大鼠的微粒体对苯并[a]芘的代谢也增加，且代谢谱与用FireMaster BP-6和Aroclor 1254诱导的微粒体所观察到的相似。
