Polychlorinated biphenyls and methylmercury act synergistically to reduce rat brain dopamine content in vitro
Polychlorinated biphenyls and methylmercury act synergistically to reduce rat brain dopamine content in vitro
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DOI：
10.2307/3454475
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发表时间：
1999-11-01
影响因子：
10.4
通讯作者：
Seegal, RF
中科院分区：
文献类型：
--
作者：
Bemis, JC;Seegal, RF
孕妇食用受污染的五大湖鱼类与婴儿和儿童出生体重下降和认知功能缺陷有关。这些鱼类含有许多已知和疑似人为神经毒物，因此难以确定哪些污染物是造成所观察到的缺陷的原因。我们已经进行了一系列的实验，以确定相关的毒物，通过比较这些污染物中的两个-多氯联苯（PCBs）和甲基汞（甲基汞）-这两个都是公认的神经毒物的神经毒性作用。从成年大鼠脑纹状体冲床暴露于多氯联苯，甲基汞，或两者的组合，和组织和介质中的多巴胺（DA）及其代谢产物的浓度进行了测定，通过高效液相色谱法。暴露于多氯联苯只减少组织DA和升高的媒体DA的剂量依赖性的方式。仅接触甲基汞对这两项措施均无显著影响。然而，当纹状体冲床同时暴露于多氯联苯和甲基汞，有显着更大的组织DA浓度和介质DA的升高比多氯联苯所造成的，在介质中的乳酸脱氢酶浓度的变化的情况下，降低。还观察到组织和培养基中3，4-二羟基苯乙酸浓度升高。我们认为这两种毒物之间的显著相互作用可能是由于共同的作用位点（即，毒素诱导的细胞内钙离子增加和第二信使系统的变化），影响DA功能。这些污染物之间的协同作用表明，未来的鱼类消费准则的修订应考虑污染物的相互作用。
Consumption of contaminated Great Lakes fish by pregnant women is associated with decreased birth weight and deficits in cognitive function in their infants and children. These fish contain many known and suspected anthropogenic neurotoxicants, making it difficult to determine which contaminant(s) are responsible for the observed deficits. We have undertaken a series of experiments to determine the relevant toxicants by comparing the neurotoxic effects of two of these contaminants-polychlorinated biphenyls (PCBs) and methylmercury (MeHg)-both of which are recognized neurotoxicants. Striatal punches obtained from adult rat brain were exposed to PCBs only, MeHg only, or the two in combination, and tissue and media concentrations of dopamine (DA) and its metabolites were determined by high performance liquid chromatography. Exposure to PCBs only reduced tissue DA and elevated media DA in a dose-dependent fashion. Exposure to MeHg only did not significantly affect either measure. However, when striatal punches were simultaneously exposed to PCBs and MeHg, there were significantly greater decreases in tissue DA concentrations and elevations in media DA than those caused by PCBs only, in the absence of changes in media lactate dehydrogenase concentrations. Elevations in both tissue and media 3,4-dihydroxyphenylacetic acid concentrations were also observed. We suggest that the significant interactions between these two toxicants may be due to a common site of action (i.e., toxicant-induced increases in intracellular calcium and changes in second messenger systems) that influences DA function. The synergism between these contaminants suggests that future revisions of fish-consumption guidelines should consider contaminant interactions.