SCNU Environmental Research Institute, Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety, MOE Key Laboratory of Theoretical Chemistry of Environment, South China Normal University, Guangzhou 510006, China; School of Environment, South China Normal University, University Town, Guangzhou 510006, China.
South China Institute of Environmental Sciences, Ministry of Ecology and Environment, Guangzhou 510535, China.
Sci Total Environ. 2024 Dec 10;955:176895. doi: 10.1016/j.scitotenv.2024.176895. Epub 2024 Oct 12.
Sodium p-perfluorous nonenoxybenzene sulfonate (OBS) is a prominent alternative to perfluorooctanesulfonic acid (PFOS). Numerous studies have demonstrated hepatotoxicity and neurotoxicity of OBS and PFOS in mammals. The lungs, as a sensitive organ, are among the potential target organs for OBS and PFOS exposure. However, their toxic effects on the lungs remain unclear. In the present study, three-dimensional (3D) spheroids constructed from A549 cells were exposed to OBS and PFOS for 7 days to evaluate pulmonary toxicity through morphological examination, growth kinetics, transcriptomic profiling, and biochemical assays. Our results showed that OBS significantly reduced the diameter, volume, and growth fraction of the spheroids compared to PFOS. Transcriptomic analysis revealed a notable enrichment of the IL-17 signaling pathway after 7 days of OBS exposure. Significant differences in the transcription of genes within this pathway were observed between OBS and PFOS exposure. OBS reduced the transcription of tnfaip3, nfkbiα, map3k8, enpp2, jun, il6, cxcl1, cxcl2, cxcl3, and cxcl8 in the IL-17 signaling pathway, while PFOS enhanced the transcription of nfkbiα. Additionally, OBS decreased the level of IL-8, whereas PFOS had a minor effect. Cluster analysis confirmed significant differences in the pulmonary toxicity between OBS and PFOS. Our study demonstrated the utility of spheroids as an in vitro cell model complemented with omics technology, for comparing the pulmonary toxicity of OBS and PFOS. It provided a novel approach for evaluating the pulmonary toxicity of new pollutants like OBS.
过氟壬基苯磺酸钠（OBS）是全氟辛烷磺酸（PFOS）的重要替代品。许多研究已经证明了 OBS 和 PFOS 在哺乳动物中的肝毒性和神经毒性。肺作为一种敏感的器官，是 OBS 和 PFOS 暴露的潜在靶器官之一。然而，它们对肺部的毒性作用尚不清楚。在本研究中，使用 A549 细胞构建的三维（3D）球体暴露于 OBS 和 PFOS 中 7 天，通过形态学检查、生长动力学、转录组谱分析和生化测定来评估肺毒性。我们的结果表明，与 PFOS 相比，OBS 显著降低了球体的直径、体积和生长分数。转录组分析显示，OBS 暴露 7 天后，IL-17 信号通路明显富集。在 OBS 和 PFOS 暴露之间，观察到该通路中基因转录的显著差异。OBS 降低了 tnfaip3、nfkbiα、map3k8、enpp2、jun、il6、cxcl1、cxcl2、cxcl3 和 cxcl8 等基因在 IL-17 信号通路中的转录，而 PFOS 增强了 nfkbiα的转录。此外，OBS 降低了 IL-8 的水平，而 PFOS 的影响较小。聚类分析证实了 OBS 和 PFOS 之间肺毒性的显著差异。本研究证明了球体作为一种补充了组学技术的体外细胞模型的实用性，用于比较 OBS 和 PFOS 的肺毒性。它为评估 OBS 等新型污染物的肺毒性提供了一种新方法。
