Rifkind A B, Muschick H
Nature. 1983;303(5917):524-6. doi: 10.1038/303524a0.
Polyhalogenated hydrocarbons are widely distributed environmental pollutants. Several members of the class, including certain polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans and dibenzodioxins, produce a characteristic toxicity syndrome, manifestations of which are increased mortality, oedema, hyperkeratosis, thymic involution and hepatotoxicity. The toxic hydrocarbons are also inducers of cytochrome P448-mediated mixed function oxidases. The toxicity and induction responses both involve initial binding of the hydrocarbon to the same cytosolic receptor, but the subsequent events are not understood. It is not known, for example, whether the toxicity and induction are causally related, or whether they are coordinated but independent aspects of a pleiotropic response. Here we report that benoxaprofen, a nonsteroidal antiinflammatory agent, decreases the toxicity of a PCB isomer, 3,4,3',4' tetrachlorobiphenyl (TCB), in the chick embryo and that it does so without altering the degree of mixed function oxidase induction. The independent alteration of PCB toxicity and induction suggests that the two phenomena are not causally related. The decrease in toxicity by benoxaprofen suggests further that products of arachidonic acid metabolism or other mediators of inflammation may have a causal role in halogenated hydrocarbon toxicity.
多卤代烃是广泛分布的环境污染物。该类物质中的几种，包括某些多氯联苯（PCBs）、多氯二苯并呋喃和二苯并二恶英，会产生一种特征性毒性综合征，其表现为死亡率增加、水肿、角化过度、胸腺萎缩和肝毒性。这些有毒碳氢化合物还是细胞色素P448介导的混合功能氧化酶的诱导剂。毒性反应和诱导反应都涉及碳氢化合物与同一胞质受体的初始结合，但后续事件尚不清楚。例如，毒性和诱导作用是否存在因果关系，或者它们是否是多效性反应中相互协调但独立的方面，目前尚不清楚。在此我们报告，非甾体抗炎药苯恶洛芬可降低鸡胚中一种多氯联苯异构体3,4,3',4'-四氯联苯（TCB）的毒性，并且在不改变混合功能氧化酶诱导程度的情况下做到了这一点。多氯联苯毒性和诱导作用的独立改变表明这两种现象没有因果关系。苯恶洛芬导致的毒性降低进一步表明，花生四烯酸代谢产物或其他炎症介质可能在卤代烃毒性中起因果作用。
