Reactive metabolites and carcinogenicity of halogenated ethylenes.
Reactive metabolites and carcinogenicity of halogenated ethylenes.
复制标题
卤化乙烯的反应代谢物和致癌性。
DOI：
10.1016/0006-2952(82)90227-1
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发表时间：
1982
影响因子：
5.8
通讯作者：
J. Filser
中科院分区：
文献类型：
--
作者：
H. Bolt;R. Laib;J. Filser
生物反应中间体是一个迅速发展的知识领域，在这方面卤化化合物，如氯乙烯，起着突出的作用[1]。对于氯化乙烯，Henschler及其同事已经发表了连接结构和活性的初步考虑[2-51]。他们提出了以下建议：(a)氯化乙烯最初通过微粒体单加氧酶转化为环氧化物（氧环烷）中间体，随后通过分子重排“解毒”（见图1）；氯烷中间体的JBF反应活性和毒性取决于氯取代的类型，对称取代使环氧化物相对稳定，不会致突变性，而不对称取代导致不稳定，因此会致突变性；(c)三氯乙烯不受此一般规则的约束，因为它的环氧化物2,2,3 -三氯醇和~ e~ alth~~~~不对称取代和反应性，在细胞色素P-450位点立即进一步转化为三氯乙醛（氯醛）。最近在3种动物中进行的一项吸入致癌性研究支持了后一种说法，该研究没有显示三氯乙烯具有致癌性。此外，原用大肠杆菌k12131获得的致突变性数据一般用S.~~~~~~ r~~~菌株[?]J. Bartsch el - ai的这项研究。[7]还包括一溴化和一溴化乙烯、乙烯基溴化和乙烯氟化：这两种不对称取代的卤代乙烯都对致突变代谢物具有生物活性，但程度大不相同。偏氟乙烯仅表现出“边际诱变性”。
A field of rapidly expanding knowledge is that of biological reactive intermediates, in this discussion halogenated compounds, eg vinyl chloride, play a prominent role [l]. For the chlorinated ethylenes, preliminary considerations connecting structure and activity have been published by Henschler and coworkers [2-51. They suggested the following:(a) a11 chlorinated ethylenes are Initially b~ otransformed by microsomal monooxygenase (s) to epoxide (oxirane) intermediates which are subsequently ‘detoxified’, eg by molecular rearrangement (see Fig. 1); jbf reactivities and hence toxicities of individual chlorooxirane intermediates depend on the type of chlorine substitution in that symmetric substitution renders the epoxide relatively stable and not mutagenic whilst asymmetric substitution causes unstable and, therefore, mutagenic epoxides;(c) trichloroethylene is exempt from this general rule because its epoxide 2, 2, 3-trichlorooxir~ e~ altho~~~~ asymmetrically substituted and reactive, is immediately further transformed at the cytochrome P-450 site to trichloroacetaldehyde (chloral). The latter is now supported by a recent inhalatory carci~ ogenicity study in 3 animal species which revealed no indication for carcino~ enicity of trichloroethylene [6]. Also, mutagenicity data originalIy obtained with E. coli K 12 131 were generalfy confirmed by using S.~~~~~~ r~~~ strains [? J. This study by Bartsch el ai.[7] also included one brominated and one~ uor~ nated ethylene, vinyl bromide and vinyiidene fluoride: both asymmetrically substituted haloethylenes were bioactivated to mutagenic metabolites, but to much different extents. Vinylidene fluoride showed only ‘marginal mutagenicity’.