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多氯联苯和多溴联苯醚以相加的方式改变发育中大鼠突触体纹状体多巴胺的神经化学。

Polychlorinated biphenyls and polybrominated diphenyl ethers alter striatal dopamine neurochemistry in synaptosomes from developing rats in an additive manner.

机构信息

Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA.

出版信息

Toxicol Sci. 2010 Nov;118(1):150-9. doi: 10.1093/toxsci/kfq229. Epub 2010 Jul 29.

Abstract

Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are widespread environmental contaminants associated with changes in behavior and neurochemical function in laboratory animals and behavioral deficits in children. PCBs and PBDEs are found in food, especially in seafood and dairy products, and coexposure to these contaminants is likely. We examined the effects of an environmentally relevant mixture of PCBs (Fox River Mix [FRM]) and a PBDE mixture (DE-71) alone and in combination on synaptosomal and medium dopamine (DA) levels and the levels of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in striatal synaptosomes derived from postnatal days (PND) 7, PND14, or PND21 rats. FRM elevated medium DA and reduced synaptosomal DA concentrations with greater potency than equimolar concentrations of DE-71. The effects of FRM, but not DE-71, were dependent on the age of the animals from which the synaptosomes were derived, with greater effects observed in synaptosomes from the youngest animals. We used Bliss' model of independence to assess the possible interaction(s) of a 1:1 mixture of FRM and DE-71 on synaptosomal DA function and found that the effects of the FRM/DE-71 mixture were additive. Furthermore, as for FRM alone, the effects of the FRM/DE71 mixture were greater in synaptosomes prepared from PND7 rats than in synaptosomes from PND14 and PND21 rats. Because the effects of these contaminants are additive, it is necessary to take into account the cumulative exposure to organohalogen contaminants such as PCBs and PBDEs during risk assessment.

摘要

多氯联苯 (PCBs) 和多溴二苯醚 (PBDEs) 是广泛存在的环境污染物,与实验动物行为和神经化学功能改变以及儿童行为缺陷有关。PCBs 和 PBDEs 存在于食物中,特别是海鲜和奶制品中,这些污染物很可能会共同暴露。我们研究了环境相关浓度的 PCBs(Fox River Mix [FRM])和 PBDE 混合物(DE-71)单独及联合作用对源自出生后第 7 天 (PND7)、第 14 天 (PND14) 或第 21 天 (PND21) 的大鼠纹状体突触体中突触体和中多巴胺 (DA) 水平以及 DA 代谢物 3,4-二羟基苯乙酸 (DOPAC) 水平的影响。FRM 升高了培养基中的 DA,降低了突触体中的 DA 浓度,其效力强于等摩尔浓度的 DE-71。FRM 的作用,而不是 DE-71 的作用,依赖于突触体来源动物的年龄,来自最小动物的突触体的作用更大。我们使用 Bliss 独立性模型来评估 FRM 和 DE-71 1:1 混合物对突触体 DA 功能的可能相互作用,发现 FRM/DE-71 混合物的作用是相加的。此外,与 FRM 单独作用一样,FRM/DE71 混合物在源自 PND7 大鼠的突触体中的作用大于源自 PND14 和 PND21 大鼠的突触体中的作用。由于这些污染物的作用是相加的,因此在风险评估中必须考虑到对有机卤代污染物(如 PCB 和 PBDE)的累积暴露。

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