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C57BL/6J小鼠肝脏中氯代芳烃之间的毒代动力学相互作用:I. 多氯联苯(PCBs)

Toxicokinetic interactions between chlorinated aromatic hydrocarbons in the liver of the C57BL/6J mouse: I. Polychlorinated biphenyls (PCBs).

作者信息

de Jongh J, Wondergem F, Seinen W, Van den Berg M

机构信息

Research Institute of Toxicology, University of Utrecht, The Netherlands.

出版信息

Arch Toxicol. 1993;67(7):453-60. doi: 10.1007/BF01969915.

Abstract

2,2',4,4',5,5'- (PCB 153), 2,3,3',4,4',5- (PCB 156) and 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169) were administered orally to three groups of C57BL/6J mice using single doses of 1.5-109.1 mg/kg. Two other groups of mice received binary mixtures of PCB 153 and 156 or PCB 153 and 169. The hepatic deposition, elimination, CYP1a and CYP2b dependent enzyme activities were studied during a 77-day period. Some interactive effects on hepatic deposition and elimination were observed, resulting in increased deposition and faster elimination. These effects were most pronounced for the PCBs 156 and 169. A potentiating effect on hepatic CYP1a dependent 7-ethoxyresorufin-O- deethylation (EROD) activity was observed for the combination of PCB 156 and 153. Based on the results from the present study and earlier studies, it is suggested that the potentiating effect on EROD activity might be caused by a mechanism that is governed by at least two factors. The first is a toxicokinetic modulation of hepatic retention. The second factor is probably an elevation of hepatic Ah receptor levels by PCB 153.

摘要

将2,2',4,4',5,5'-六氯联苯(多氯联苯153)、2,3,3',4,4',5-六氯联苯(多氯联苯156)和3,3',4,4',5,5'-六氯联苯(多氯联苯169)以1.5 - 109.1毫克/千克的单剂量经口给予三组C57BL/6J小鼠。另外两组小鼠接受多氯联苯153与156或多氯联苯153与169的二元混合物。在77天的时间段内研究了肝脏沉积、消除、细胞色素P450 1A(CYP1a)和细胞色素P450 2B(CYP2b)依赖性酶活性。观察到对肝脏沉积和消除有一些交互作用,导致沉积增加和消除加快。这些作用在多氯联苯156和169中最为明显。观察到多氯联苯156与153的组合对肝脏CYP1a依赖性7-乙氧基异吩恶唑酮-O-脱乙基酶(EROD)活性有增强作用。根据本研究和早期研究的结果,提示对EROD活性的增强作用可能由至少两个因素控制的机制引起。第一个因素是肝脏潴留的毒代动力学调节。第二个因素可能是多氯联苯153使肝脏芳烃受体水平升高。

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