Neurochemical effects of polychlorinated biphenyls: an overview and identification of research needs.
Neurochemical effects of polychlorinated biphenyls: an overview and identification of research needs.
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发表时间：
1997
期刊：
影响因子：
3.4
通讯作者：
H. Tilson;Kodavanti Pr
中科院分区：
文献类型：
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作者：
H. Tilson;Kodavanti Pr
多氯联苯是卤代烃类环境化学品的成员，包括二苯并呋喃和二恶英。多氯联苯在40年的时间里被用于多种工业用途。它们在生态系统和野生动物生物样本中的出现，以及意外中毒的记录案例，导致其在1977年被禁止生产。多氯联苯继续受到环境毒理学家的关注，因为它们在环境中的持久性，并报告说，暴露于相对较低的水平可能与微妙的行为和神经缺陷有关，特别是如果暴露发生在发育期间。据报告，多氯联苯对人类的神经发育具有毒性，并在包括非人类灵长类动物在内的几种实验动物中得到证实。在过去的20年里，人们一直试图了解多氯联苯诱导的动物模型中的行为和神经影响的细胞基础。成年动物暴露于一个单一的，相对较高剂量的多氯联苯降低了几个脑神经递质的含量，而重复暴露于较低剂量的多氯联苯似乎会影响大脑DA代谢。PCB影响DA的机制尚不清楚。目前已知，某些多氯联苯同源物的结构配置与其他多氯化合物（包括2，3，7，8-四氯二苯并对二恶英）一样，有利于与芳烃受体结合。另一方面，某些多氯联苯同系物具有结构特征，例如，非共面性，这减少了对Ah受体的访问。在体内暴露后出现在大脑中的非TCDD样PCB同系物在体外降低PC-12细胞中的DA含量和抑制钙稳态机制方面表现出最高的效力。多氯联苯对DA含量或钙稳态的影响的生物学意义，在体内发育暴露后观察到的行为和神经影响尚不清楚。然而，最近的研究表明，多氯联苯可以改变一些可能对发育很重要的生理过程。例如，多氯联苯在发育过程中引起的甲状腺功能改变可能是多氯联苯在人类和动物模型中报告的一些发育影响的基础。看来有必要在若干领域对多氯联苯进行进一步研究，包括：1）与Ah-R结合所必需的结构要求，2）PCB诱导的体外DA含量和钙稳态改变的机制，3）观察到的体外神经化学效应与体内效应之间的关系，（4）多氯联苯诱导的神经化学效应与甲状腺激素发育等重要发育过程之间的关系。
The PCBs are members of the halogenated hydrocarbon class of environmental chemicals that includes the dibenzofurans and dioxins. The PCBs were used over a period of 40 years for number of industrial purposes. Their appearance in the ecosystem and biological samples from wildlife, as well as documented cases of accidental poisoning led to the banning of their manufacture in 1977. The PCBs continue to be of concern to environmental toxicologists because of their persistence in the environment and reports that exposure to relatively low levels may be associated with subtle behavioral and neurological deficits, particularly if exposure occurs during development. Developmental neurotoxicity of PCBs has been reported in humans and confirmed in several laboratory animal species, including non-human primates. During the last 20 years, there has been an attempt to understand the cellular bases of PCB-induced behavioral and neurological effects in animal models. Exposure of adult animals to a single, relatively high dose of PCBs decreases the content of several brain neurotransmitters, while repeated exposure to lower PCB doses appears to affect brain DA metabolism. The mechanism by which PCB affects DA remains unclear. It is now known that some PCB congeners have a structural configuration that facilitates binding to an aryl hydrocarbon (Ah) receptor like other polychlorinated compounds, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Some PCB congeners, on the other hand, have structural characteristics, e.g., non-coplanarity, that diminish access to the Ah receptor. Non-TCDD-like PCB congeners that appear in the brain following in vivo exposure demonstrate the highest potency in terms of decreasing DA content in PC-12 cells and inhibiting calcium homeostasis mechanisms in vitro. The biological significance of the effects of the PCBs on DA content or calcium homeostasis with regard to the behavioral and neurological effects observed following developmental exposure in vivo is not clear. Recent research, however, suggests that PCBs can alter a number of physiological processes that may be important for development. For example, PCB-induced alterations in thyroid function during development may underlie some of the developmental effects of PCBs reported in humans and animal models. Additional research on the PCBs seems warranted in a number of areas, including the: 1) structural requirements necessary for binding to the Ah-receptor, 2) mechanism(s) of PCB-induced alterations in DA content and calcium homeostasis in vitro, 3) relationship between observed neurochemical effects in vitro and effects in vivo, and 4) relationship between PCB-induced neurochemical effects and crucial developmental processes such as those controlled by thyroid hormone development.