Metabolism of polychlorinated biphenyls by Gunn rats: Identification and serum retention of catechol metabolites
Metabolism of polychlorinated biphenyls by Gunn rats: Identification and serum retention of catechol metabolites
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DOI：
10.1021/tx0498096
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发表时间：
2004-12-01
影响因子：
4.1
通讯作者：
Degawa, M
中科院分区：
文献类型：
--
作者：
Haraguchi, K;Kato, Y;Degawa, M
研究了2，4，5，2 '，5'-五氯联苯（CB 101）和商用多氯联苯混合物Kanechlor-500（KC 500）暴露于Wistar大鼠和尿苷二磷酸葡萄糖醛酸基转移酶（UGT）纯合缺陷型古恩大鼠体内多氯联苯（PCBs）持久性代谢产物的组织分布。暴露于CB 101后，在肝、肺、肾、血液和脂肪组织中检测到四种羟基和两种甲磺酰基（MeSO 2）代谢产物。其中一个被鉴定为3 '，4'-（OH）（2）-2，4，5，2 '，5'-pentaCB，其选择性地保留在古恩大鼠的血清中。对暴露于KC 500后两种大鼠品系中的代谢物谱的比较分析显示，古恩大鼠肝脏中几种二羟基PCB代谢物的形成率较高;主要代谢物是来自2，5，3 '，4'-tetraCB、CB 101、2，3，6，3 '，4'-pentaCB和2，3，6，2 '，4'，5 '-pentaCB的儿茶酚。因此，古恩大鼠有效地代谢多氯联苯与2，5-或2，5，6-氯取代的3，4-邻苯二酚，但较少形成的MeSO 2代谢物在肝脏中。虽然两种大鼠品系都保留了血清中的4-OH-2，3，5，3 '，4'-pentaCB，但古恩大鼠也保留了儿茶酚PCBs，约占总酚PCBs的52%。这些结果表明，缺乏UGT显着改变的形成率和保留配置文件的儿茶酚和MeSO 2代谢产物的多氯联苯。
The tissue distributions of persistent metabolites of polychlorinated biphenyls (PCBs) in Wistar rats and homozygous uridine diphosphate glucuronosyltransferase (UGT) deficient Gunn rats exposed to 2,4,5,2',5'-pentachlorobiphenyl (CB101) and the commercial PCB mixture, Kanechlor-500 (KC500), were investigated. After exposure to CB101, four hydroxy and two methylsulfonyl (MeSO2) metabolites were detected in liver, lung, kidney, blood, and adipose tissues. One was identified as 3',4'-(OH)(2)-2,4,5,2',5'-pentaCB, which was retained selectively in the serum of Gunn rats. Comparative analysis of the metabolite profiles in both rat strains after exposure to KC500 showed higher formation ratios of several dihydroxy PCB metabolites in the liver of Gunn rats; major metabolites are the catechols from 2,5,3',4'-tetraCB, CB101, 2,3,6,3',4'-pentaCB, and 2,3,6,2',4',5'-pentaCB. Thus, Gunn rats effectively metabolized PCBs with 2,5- or 2,5,6-chlorine substitution to the 3,4-catechol, but less formed MeSO2 metabolites in the liver. Although both rat strains retained 4-OH-2,3,5,3',4'-pentaCB in serum, Gunn rats also retained the catechol PCBs, accounting for about 52% of the total phenolic PCBs. These results suggest that a lack of UGTs markedly alters the formation ratios and retention profiles of catechols and MeSO2 metabolites of PCBs.