Halogenated biphenyls: molecular toxicology.
Halogenated biphenyls: molecular toxicology.
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卤代联苯：分子毒理学。
DOI：
10.1139/y82-151
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发表时间：
1982
影响因子：
2.1
通讯作者：
M. Campbell
中科院分区：
文献类型：
--
作者：
S. Safe;L. Robertson;L. Safe;A. Parkinson;S. Bandiera;T. Sawyer;M. Campbell
多氯联苯的生物效应和毒性效应与其结构密切相关。毒性最大的多氯联苯，即3，3‘，4，4’-四-，3，3‘，4，4’，5-五-和3，3‘，4，4’，5，5‘-六氯联苯在两个苯环上的至少一个间位和对位(即侧位)上被取代，不含邻氯取代基。这三个同系物和第四个PCB3，4，4‘，5-四氯联苯是2，3，7，8-四氯二苯并对二恶英(TCDD)的近似异构体，与TCDD一样，在培养的大鼠和大鼠肝癌细胞中诱导肝微粒体苯并[a]芘或芳烃羟化酶(AHH)。四个侧向取代的PCBs的单邻位取代类似物也能诱导微粒体AHH活性，同时增强微粒体酶活性，这是苯巴比妥(PB)所能诱导的。这组多氯联苯显示出2，3，7，8-TCDD和相关的多氯二苯并-对二恶英的许多性质；这些多氯联苯对AHH诱导的相对效力和它们与ah受体蛋白的结合亲和力非常相似，其中一些多氯联苯也是有毒的。对其他卤代联苯的初步研究证实，侧链取代基的极化率是它们作为AHH诱导剂活性的一个重要因素(即I大于Br大于CI大于F)。然而，对其他取代卤代联苯的初步结果表明，额外的结构因素在确定这些化合物的活性方面也是重要的。
The biologic and toxic effects of polychlorinated biphenyls (PCBs) are remarkably dependent on their structure. The most toxic PCBs, namely 3,3',4,4'-tetra-, 3,3',4,4',5-penta- and 3,3',4,4',5,5'-hexachlorobiphenyl are substituted in at least one meta and para position on both phenyl rings (i.e., the lateral positions) and contain no ortho-chloro substituents. These three congeners and a fourth PCB, namely 3,4,4',5-tetrachlorobiphenyl, are approximate isostereomers of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and, in common with TCDD, induce hepatic microsomal benzo[a]pyrene or aryl hydrocarbon hydroxylase (AHH) in rats and rat hepatoma cells in culture. The mono-ortho substituted analogs of the four laterally substituted PCBs also induce microsomal AHH activity and simultaneously enhance microsomal enzyme activities which are inducible by phenobarbitone (PB). This group of PCBs exhibits many of the properties of 2,3,7,8-TCDD and related polychlorinated dibenzo-p-dioxins; there is a close parallel in the relative potencies of these PCBs for AHH induction and their binding affinities for the Ah receptor protein and some of these PCBs are also toxic. Preliminary studies on other halogenated biphenyls confirm that the polarizability of a lateral substituent is an important factor in their activity as AHH inducers (i.e., I greater than Br greater than Cl greater than F). However, preliminary results with other substituted halogenated biphenyls suggest that additional structural factors are also important in determining the activity of these compounds.