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新型全氟辛烷磺酸替代品 OBS 对斑马鱼发育的毒性:重点关注纤毛破坏。

Developmental toxicity of the novel PFOS alternative OBS in developing zebrafish: An emphasis on cilia disruption.

机构信息

College of Environment, Zhejiang University of Technology, Hangzhou 310032, China; Research Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330012, China.

College of Environment, Zhejiang University of Technology, Hangzhou 310032, China.

出版信息

J Hazard Mater. 2021 May 5;409:124491. doi: 10.1016/j.jhazmat.2020.124491. Epub 2020 Nov 5.

DOI:10.1016/j.jhazmat.2020.124491
PMID:33223314
Abstract

In recent years, sodium p-perfluorous nonenoxybenzene sulfonate (OBS) has emerged as a substitute for PFOS with large demand and application in the Chinese market. However, little is known about potential developmental effects of OBS. In this study, zebrafish embryos were acutely exposed to different concentrations of OBS and the positive control PFOS for a comparative developmental toxicity assessment. OBS caused hatching delays, body axis curvature, neurobehavioral inhibition and abnormal cardiovascular development. These organismal effects were accompanied by change of development related genes expression profile, in which some cases were similar to PFOS. Overall, the toxic effects induced by OBS were generally milder than that of PFOS. Further investigation suggested that both OBS and PFOS disrupted ciliogenesis, evidenced by the ciliary immunostaining, changes in gene expression of kinesin family, dynein arm family and tubulin family members, as well as downregulation of the abundance of motor proteins including KIF3C, DYNC1H1 and DYNC1LI1. The influence of PFOS was stronger than that of OBS on ciliary genes and proteins. Molecular docking analysis revealed that both OBS and PFOS fitted into the motor proteins tightly, but binding affinity between OBS and motor proteins was lower than PFOS. Collectively, OBS and PFOS may act on ciliary motor proteins to interfere with ciliogenesis, leading to ciliary dysfunction and providing a novel probable action mode linked to developmental toxicity. This raises concerns regarding the health risks of the novel PFOS alternative OBS.

摘要

近年来,全氟辛基磺酸钠(PFOS)的替代品——对氟辛基苯磺酸钠(OBS)在我国市场上的需求和应用日益增长。然而,对于 OBS 的潜在发育毒性知之甚少。本研究采用急性染毒的方式,对比研究了 OBS 和阳性对照物 PFOS 对斑马鱼胚胎的发育毒性。结果显示,OBS 暴露引起斑马鱼胚胎孵化延迟、体轴弯曲、神经行为抑制和心血管发育异常等表型。同时,OBS 暴露还导致了与发育相关基因表达谱的改变,其中部分情况与 PFOS 相似。整体而言,OBS 引起的毒性效应通常比 PFOS 更为温和。进一步研究表明,OBS 和 PFOS 均能破坏纤毛发生,这一现象可通过纤毛免疫染色、驱动蛋白家族、动力蛋白臂家族和微管家族成员基因表达的改变,以及包括 KIF3C、DYNC1H1 和 DYNC1LI1 在内的动力蛋白丰度的下调来证实。与 OBS 相比,PFOS 对纤毛基因和蛋白的影响更为显著。分子对接分析表明,OBS 和 PFOS 均可与驱动蛋白紧密结合,但 OBS 与驱动蛋白的结合亲和力低于 PFOS。综上,OBS 和 PFOS 可能通过作用于纤毛运动蛋白来干扰纤毛发生,导致纤毛功能障碍,并为其发育毒性提供了一种新的可能作用模式。这引发了对新型 PFOS 替代品 OBS 的健康风险的关注。

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