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围生期接触高纯度多氯联苯同系物(PCB52 和 PCB180)对成年大鼠多巴胺依赖性行为的影响。

Dopamine-dependent behavior in adult rats after perinatal exposure to purity-controlled polychlorinated biphenyl congeners (PCB52 and PCB180).

出版信息

Toxicol Lett. 2014 Jan 3;224(1):32-9.

Abstract

Since knowledge about toxic effects of non-dioxinlike (NDL) PCBs is fragmentary, regulatory panels have concluded that risk assessment of these congeners is hampered or impossible. As the dopaminergic system is one of the main targets in PCB-related neurotoxic effects after developmental exposure, we selected catalepsy induced by the dopamine receptor blocker haloperidol to characterize effects of the NDL congeners PCB52 and PCB180 in adult offspring from exposed rat dams. Rat dams were treated with PCB congeners by gavage using six dose levels (total doses: PCB52 - 0, 30, 100, 300, 1000 or 3000 mg/kg body wt.; PCB180 - 0, 10, 30, 100, 300, or 1000 mg/kg body wt.) to allow benchmark dose analysis of the results. Testing of adult offspring (starting at 180 days of age) for catalepsy induced by injection with haloperidol revealed slightly prolonged latencies to movement onset in female offspring exposed to PCB52. Exposure to PCB180 resulted in more pronounced effects, with generally reduced latencies in male offspring. These results indicate reduced dopaminergic activity after PCB52 exposure, whereas the outcome for PCB180 may be related to increased extracellular dopamine as reported in the literature.Benchmark dose analyses revealed that both PCB congeners exerted effects mainly at moderate exposure levels. Together, these results underline the importance of effects on the dopaminergic system as indicated by studies in human females after occupational PCB exposure.

摘要

由于非二恶英类(NDL)多氯联苯的毒性作用知识零碎,监管小组得出结论,这些同系物的风险评估受到阻碍或不可能。由于多巴胺能系统是发育暴露后与多氯联苯相关的神经毒性作用的主要靶标之一,我们选择了多巴胺受体阻断剂氟哌啶醇引起的僵住来表征 NDL 同系物 PCB52 和 PCB180 在暴露于母体多氯联苯的成年后代中的作用。通过灌胃用六种剂量水平(总剂量:PCB52-0、30、100、300、1000 或 3000mg/kg 体重;PCB180-0、10、30、100、300 或 1000mg/kg 体重)用母体多氯联苯处理大鼠,以允许对结果进行基准剂量分析。用氟哌啶醇注射测试成年后代(从 180 天大开始)的僵住,发现暴露于 PCB52 的雌性后代的运动起始潜伏期略有延长。暴露于 PCB180 导致更明显的影响,雄性后代的潜伏期通常降低。这些结果表明,PCB52 暴露后多巴胺能活性降低,而 PCB180 的结果可能与文献中报道的细胞外多巴胺增加有关。基准剂量分析表明,两种多氯联苯主要在中度暴露水平下发挥作用。这些结果共同强调了职业性多氯联苯暴露后对多巴胺能系统的影响的重要性。

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