Studies on the microsomal metabolism and binding of polybrominated biphenyls (PBBs).
Studies on the microsomal metabolism and binding of polybrominated biphenyls (PBBs).
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多溴联苯（PBB）的微粒体代谢和结合研究。
DOI：
10.2307/3428741
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发表时间：
1978
影响因子：
10.4
通讯作者：
S. Aust
中科院分区：
文献类型：
--
作者：
G. Dannan;R. Moore;S. Aust
利用大鼠肝微粒体研究了多溴联苯（PBBs）在NADPH和O2存在下的体外代谢。在与对照或3-甲基胆蒽（MC）诱导的微粒体孵育后，获得了所有多溴联苯的定量回收率。在12种主要成分中，在与苯巴比妥（PB）或多溴联苯醚（PBBS）预处理大鼠的微粒体孵育后，仅观察到峰1（2，4，5，2 '，5'-五溴代二苯）和峰3（六溴代二苯）损失。在七种结构上确定的多溴联苯成分中，只有峰1具有无溴帕拉。峰1、2和5都有两个相邻的未取代碳，但只有峰1被代谢。在所研究的两种二溴联苯模型化合物中，2，2 '-同系物被PB诱导的微粒体非常迅速地代谢，而其4，4'-异构体则不然。这些结果表明，存在一个自由帕拉对位溴联苯的代谢所需的。不太重要的似乎是溴的数量或两个相邻的未取代碳的可用性。肝脏和乳汁提取物中峰1和峰3的水平急剧降低也提供了峰1和峰3代谢的体内证据。将几乎完全由峰4（2，4，5，2 '，4'，5 '-六溴代二苯）和峰8（2，3，4，5，2'，4 '，5'-七溴代二苯）组成的14 C-PBB混合物与PB或PBBs诱导的微粒体和NADPH一起孵育时，在大量提取后微粒体中仅残留痕量放射性。然而，与MC预处理大鼠或尤其是对照大鼠微粒体结合的放射性较少。无论使用何种类型的微粒体，均未发现放射性与相似微粒体孵育中包含的外源性DNA结合。在相同的条件下，[3 H]-苯并[a]芘代谢物与DNA结合，多溴联苯诱导的微粒体增强这种结合超过6倍。
The metabolism of polybrominated biphenyls (PBBs) was studied in vitro by using rat liver microsomes in the presence of NADPH and atmospheric O2. Quantitative recoveries of all PBBs were obtained after incubations with control or 3-methylcholanthrene (MC) induced microsomes. Of the twelve major components, losses of only peaks 1 (2,4,5,2',5'-pentabromobiphenyl) and 3 (a hexabromobiphenyl) were observed following incubations with microsomes from phenobarbital (PB)- or PBBS- pretreated rats. Of seven structurally identified PBB components, only peak 1 has a bromine-free para position. Peaks 1, 2, and 5 all have two adjacent unsubstituted carbons, yet only peak 1 is metabolized. Of two dibromobiphenyl model compounds studied, the 2,2'-congener was very rapidly metabolized by PB-induced microsomes whereas its 4,4'-isomer was not. These results suggest that the presence of a free para position is required for the metabolism of brominated biphenyls. Of lesser importance appears to be the number of bromines or the availability of two adjacent unsubstituted carbons. In vivo evidence for the metabolism of peaks 1 and 3 was also provided by their drastically diminished levels in liver and milk extracts. When a 14C-PBB mixture consisting almost exclusively of peaks 4 (2,4,5,2',4',5'-hexabromobiphenyl) and 8 (2,3,4,5,2',4',5'-heptabromobiphenyl) was incubated with PB- or PBBs- induced microsomes and NADPH, only traces of radioactivity remained with the microsomes after extensive extraction. However, less radioactivity was bound to microsomes from MC pretreated or especially control rats. No radioactivity was bound to exogenous DNA included in similar microsomal incubations, regardless of the type of microsomes used. Under the same conditions, [3H]-benzo[a]pyrene metabolites were bound to DNA, and PBB-induced microsomes enhanced this binding more than six-fold.