Metabolism of [14C]- and [36C]-labeled vinyl chloride in vivo and in vitro.
Metabolism of [14C]- and [36C]-labeled vinyl chloride in vivo and in vitro.
复制标题
[14C]-和[36C]-标记的氯乙烯在体内和体外的代谢。
DOI：
10.1016/0006-2952(79)90140-0
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发表时间：
1979
影响因子：
5.8
通讯作者：
P. Watanabe
中科院分区：
文献类型：
--
作者：
F. Guengerich;P. Watanabe
标签从[14C]氯乙烯共价结合蛋白和核酸，在存在大鼠肝微粒体部分或高纯度的细胞色素P-450和nadph -细胞色素P-450还原酶制剂。结合物与总非挥发性代谢物的比例在从体内微粒体到纯化系统的过程中增加。[36Cl]氯乙烯被微粒体和高度纯化的系统代谢：没有标签结合，大多数可以被认为是氯离子。苯巴比妥预处理大鼠在10或250 ppm暴露水平下均未诱导氯乙烯体内总代谢；然而，与蛋白质和RNA的结合在10 ppm而不是250 ppm水平下增强。苯巴比妥预处理增加了它们的卵质体中氯乙烯向总代谢物和结合代谢物的转化。在肝脏的微粒体部分中回收了相当一部分在体内代谢的[14C]氯乙烯标签，但体外培养的十二烷基硫酸钠聚丙烯酰胺凝胶电泳表明，代谢物分布在许多微粒体蛋白质中，而不是定位于细胞色素P-450。获得了怀疑氯乙烯代谢物环氧乙烷通过微粒体环氧化物水合酶代谢的证据。然而，环氧化物水合酶抑制剂3,3,3-三氯环氧丙烷，它阻断了氯乙烯的微粒体降解，并没有提高与蛋白质或腺苷结合的氯乙烯水平。
Label from [14C]vinyl chloride was covalently bound to protein and nucleic acidsin vivoandin vitroin the presence of rat liver microsomal fractions or highly purified cytochrome P-450 and NADPH-cytochrome P-450 reductase preparations. The ratio of bound to total non-volatile metabolites increased in going from thein vivoto the microsomal to the purified system. [36Cl]vinyl chloride was metabolized by microsomes and highly purified systems: no label was bound and most could be accounted for as chloride ion. Phenobarbital pretreatment of rats did not induce total metabolism of vinyl chloridein vivoat either 10 or 250 ppm exposure levels; however, binding to protein and RNA was enhanced at the 10 ppm but not the 250 ppm level. Phenobarbital pretreatment increased thein vitromicrosomal conversion of vinyl chloride to both total and bound metabolites. A sizeable fraction of the label of [14C]vinyl chloride metabolizedin vivowas recovered in the microsomal fraction of the liver, but sodium dodecyl sulfate polyacrylamide gel electrophoresis ofin vitroincubations indicated that the metabolites were distributed among many microsomal proteins and not localized to cytochrome P-450. Evidence was obtained for the metabolism of the suspected vinyl chloride metabolite chloroethylene oxide by microsomal epoxide hydratase. However, the epoxide hydratase inhibitor 3,3,3-trichloropropylene oxide, which blocks the microsomal degradation of chloroethylene oxide, did not enhance the level of vinyl chloride bound to either protein or adenosine.