Yangtze finless porpoises (YFP) accumulate high levels of per- and polyfluoroalkyl substances (PFASs). However, the health impacts of PFASs to YFP are still unknown because it is technically and ethically unfeasible to use the critically endangered YFP in toxicological exposures. To uncover the potential toxicities of PFASs to YFP, this study exposed a YFP umbilical cord fibroblast cell line to perfluorobutane sulfonate (PFBS), an emerging PFASs pollutant in the aquatic environments. After exposure, the cytotoxicity and mechanisms of PFBS were explored. Our preliminary experiments found that PFBS compromised the cell viability in a concentration and duration dependent manner. In an exposure of 48-h duration, the maximum no observed effect concentration (NOEC) of PFBS was determined to be 400 µM. High-throughput proteomics were then conducted to identify the differentially expressed proteins in YFP cells exposed to 400 µM PFBS for 48 h. The results found that PFBS exposure significantly perturbed the proteome fingerprints of YFP umbilical cord fibroblast cells. Functional annotation of differential proteins showed that PFBS had the potential to impair a variety of biological processes associated with the immunity, oxidative stress, metabolism, and proteolysis. Consistently, the intracellular levels of reactive oxygen species (ROS) and proinflammatory cytokine IL-1β were significantly increased by PFBS in YFP umbilical cord fibroblast cells. Overall, this study highlights the toxic effects of emerging PFASs on YFP and provides reference data to evaluate the health risks of aquatic pollution under the context of national YFP protection. To our knowledge, this is the first omics study using YFP umbilical cord fibroblast cells in ecotoxicology of PFASs, which is applicable to various cetacean species and pollutants.

中文翻译：

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全氟丁烷磺酸盐 （PFBS） 在长江江豚脐带成纤维细胞中的细胞毒性及机制


长江江豚 （YFP） 积累了高水平的全氟烷基和多氟烷基物质 （PFAS）。然而，PFAS 对 YFP 的健康影响仍然未知，因为在毒理学暴露中使用极度濒危的 YFP 在技术和伦理上都是不可行的。为了揭示 PFAS 对 YFP 的潜在毒性，本研究将 YFP 脐带成纤维细胞系暴露于全氟丁烷磺酸盐 （PFBS），这是水生环境中一种新兴的 PFAS 污染物。暴露后，探讨 PFBS 的细胞毒性和机制。我们的初步实验发现，PFBS 以浓度和持续时间依赖性方式损害细胞活力。在 48 小时的暴露持续时间中，PFBS 的最大无观察到效应浓度 （NOEC） 被确定为 400 μM。然后进行高通量蛋白质组学以鉴定暴露于 400 μM PFBS 48 小时的 YFP 细胞中的差异表达蛋白。结果发现，PFBS 暴露显着扰乱了 YFP 脐带成纤维细胞的蛋白质组指纹。差异蛋白的功能注释表明，PFBS 有可能损害与免疫、氧化应激、代谢和蛋白水解相关的多种生物过程。一致地，PFBS 显着增加了 YFP 脐带成纤维细胞中活性氧 （ROS） 和促炎细胞因子 IL-1β 的细胞内水平。总体而言，本研究强调了新出现的 PFAS 对 YFP 的毒性影响，并为在国家 YFP 保护的背景下评估水生污染的健康风险提供了参考数据。 据我们所知，这是首次使用 YFP 脐带成纤维细胞进行 PFAS 生态毒理学的组学研究，适用于各种鲸类物种和污染物。