Developmental neurotoxicity of perfluorinated chemicals modeled in vitro.
Developmental neurotoxicity of perfluorinated chemicals modeled in vitro.
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DOI：
10.1289/ehp.11253
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发表时间：
2008-06
影响因子：
10.4
通讯作者：
Seidler FJ
中科院分区：
文献类型：
--
作者：
Slotkin TA;MacKillop EA;Melnick RL;Thayer KA;Seidler FJ
全氟烷基酸及其衍生物在野生动物和人类体内的广泛检测，以及它们进入未成熟大脑的情况，日益引起人们对这些物质是否可能是发育中的神经毒物的关注。我们评估了全氟辛烷磺酸（PFOS）、全氟辛酸（PFOA）、全氟辛烷磺酰胺（PFOSA）和全氟丁烷磺酸（PFBS）在未分化和正在分化的PC12细胞中的作用，PC12是一种用于表征神经毒性的神经表型细胞系。我们评估了DNA合成的抑制，细胞数量和生长的缺陷，氧化应激，细胞活力降低，以及向多巴胺（DA）和乙酰胆碱（ACh）神经递质表型分化或远离的转变。总的来说，不良反应的排序顺序为PFOSA > PFOS > PFBS≈PFOA。然而，叠加在这个方案上，各种药物在其潜在机制和具体结果上有所不同。值得注意的是，PFOS以牺牲DA表型为代价促进了ACh表型的分化，PFBS抑制了两种表型的分化，PFOSA增强了两种表型的分化，PFOA对表型规范的影响很小或没有影响。这些发现表明，所有的全氟化学物质对神经发育的影响是不一样的，不太可能有一个简单的、共同的机制来产生它们的影响。我们的结果加强了体外模型的潜力，以帮助快速和具有成本效益的筛选在同一类别的不同化学物质之间的比较效果，并与已知的发育神经毒物有关。
The widespread detection of perfluoroalkyl acids and their derivatives in wildlife and humans, and their entry into the immature brain, raise increasing concern about whether these agents might be developmental neurotoxicants. We evaluated perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonamide (PFOSA), and perfluorobutane sulfonate (PFBS) in undifferentiated and differentiating PC12 cells, a neuronotypic line used to characterize neurotoxicity. We assessed inhibition of DNA synthesis, deficits in cell numbers and growth, oxidative stress, reduced cell viability, and shifts in differentiation toward or away from the dopamine (DA) and acetylcholine (ACh) neurotransmitter phenotypes. In general, the rank order of adverse effects was PFOSA > PFOS > PFBS ≈ PFOA. However, superimposed on this scheme, the various agents differed in their underlying mechanisms and specific outcomes. Notably, PFOS promoted differentiation into the ACh phenotype at the expense of the DA phenotype, PFBS suppressed differentiation of both phenotypes, PFOSA enhanced differentiation of both, and PFOA had little or no effect on phenotypic specification. These findings indicate that all perfluorinated chemicals are not the same in their impact on neurodevelopment and that it is unlikely that there is one simple, shared mechanism by which they all produce their effects. Our results reinforce the potential for in vitro models to aid in the rapid and cost-effective screening for comparative effects among different chemicals in the same class and in relation to known developmental neurotoxicants.
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影响因子：
10.4
作者：
Calafat, Antonia M;Wong, Lee-Yang;Kuklenyik, Zsuzsanna;Reidy, John A;Needham, Larry L
通讯作者：
Needham, Larry L
影响因子：
2.9
作者：
Crumpton, TL;Seidler, FJ;Slotkin, TA
通讯作者：
Slotkin, TA
影响因子：
4.2
作者：
Guan, ZZ;Yu, WF;Nordberg, A
通讯作者：
Nordberg, A
影响因子：
3.3
作者：
BELL, JM;WHITMORE, WL;SLOTKIN, TA
通讯作者：
SLOTKIN, TA
影响因子：
7.6
作者：
Jameson, Ruth R.;Seidler, Frederic J.;Slotkin, Theodore A.
通讯作者：
Slotkin, Theodore A.