Ishida C, Koga N, Hanioka N, Saeki H K, Yoshimura H
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
J Pharmacobiodyn. 1991 May;14(5):276-84. doi: 10.1248/bpb1978.14.276.
Metabolism of two polychlorinated biphenyls, 3,4,3',4'- and 2,5,2',5'-tetrachlorobiphenyl (TCB), was studied using rat liver microsomes and the four forms of cytochrome P-450 (P-450), P-450b, P-450e, P-450c and P-450d. At first, effects of various inducers of P-450 such as phenobarbital (PB), 3-methylcholanthrene (MC), isosafrole (ISF) and pregnenolone 16 alpha-carbonitrile on the formation of metabolites of these TCBs by liver microsomes were compared. 3,4,3',4'-TCB was significantly metabolized by liver microsomes from MC-treated rats to form two previously reported metabolites, 4-hydroxy-3,5,3',4'-TCB and 5-hydroxy-3,4,3',4'-TCB with a relative ratio of 2.5:1. Incubation with microsomes from untreated or PB-treated rats produced none of the metabolites. On the other hand, 2,5,2',5'-TCB was metabolized to 3-hydroxy-2,5,2',5'-TCB most easily by liver microsomes from PB-treated rats and at a moderate rate by liver microsomes from ISF-treated rats. Activities of microsomes from untreated or MC-treated rats to hydroxylate 2,5,2',5'-TCB were low or undetectable. When these TCB hydroxylase activities were examined with a reconstituted system consisting of each P-450, reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P-450 reductase, dilauroylphosphatidylcholine and NADPH-generating system, only P-450c catalyzed both the 4- and 5-hydroxylations of 3,4,3',4'-TCB at a ratio of 2.2:1. On the contrary, the hydroxylation of 2,5,2',5'-TCB proceeded efficiently with P-450b and P-450e, being more efficient with the former. P-450d did not show any catalytic activity toward 3,4,3',4'-TCB and 2,5,2',5'-TCB.(ABSTRACT TRUNCATED AT 250 WORDS)
利用大鼠肝微粒体及细胞色素P - 450的四种形式（P - 450b、P - 450e、P - 450c和P - 450d），研究了两种多氯联苯3,4,3',4'-四氯联苯（TCB）和2,5,2',5'-四氯联苯的代谢情况。首先，比较了多种细胞色素P - 450诱导剂，如苯巴比妥（PB）、3 - 甲基胆蒽（MC）、异黄樟素（ISF）和孕烯醇酮16α - 腈对这些TCB经肝微粒体形成代谢产物的影响。3,4,3',4'-TCB被MC处理大鼠的肝微粒体显著代谢，形成两种先前报道的代谢产物4 - 羟基 - 3,5,3',4'-TCB和5 - 羟基 - 3,4,3',4'-TCB，相对比例为2.5:1。与未处理或PB处理大鼠的微粒体孵育未产生任何代谢产物。另一方面，2,5,2',5'-TCB最易被PB处理大鼠的肝微粒体代谢为3 - 羟基 - 2,5,2',5'-TCB，被ISF处理大鼠的肝微粒体以中等速率代谢。未处理或MC处理大鼠的微粒体对2,5,2',5'-TCB进行羟基化的活性较低或无法检测到。当用由每种细胞色素P - 450、还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）-细胞色素P - 450还原酶、二月桂酰磷脂酰胆碱和NADPH生成系统组成的重组系统检测这些TCB羟化酶活性时，只有P - 450c以2.2:1的比例催化3,4,3',4'-TCB的4 - 和5 - 羟基化反应。相反，2,5,2',5'-TCB的羟基化反应在P - 450b和P - 450e作用下高效进行，前者更高效。P - 450d对3,4,3',4'-TCB和2,5,2',5'-TCB未表现出任何催化活性。（摘要截短于250字）
