송수민 (성균관대학교)

이상규 (성균관대학교)

송수민 (성균관대학교)

안지아 (성균관대학교)

이서영 (성균관대학교)

Rajan Thapa (성균관대학교)

이상규 (성균관대학교)

 Perfluoroalkyl substances (PFAS) pose persistent health risks due to high bioaccumulation and toxicity, underscored by the recent reclassification of PFOA as a human carcinogen. Inhaled PFAS substantially build up in lung tissue; however, the precise molecular mechanisms triggering toxicity in lung fibroblasts, essential drivers of tissue repair and fibrosis, have received little attention. This study evaluated the cytotoxicity of four PFASs (PFOA, PFNA, PFDA, and PFunDA) with varying carbon chain lengths in human lung fibroblasts (WI-38) and investigated proteomic alterations via toxicoproteomics. CCK-8 assay results showed half-maximal inhibitory concentration (IC₅₀) values of 489 µM (PFOA), 386 µM (PFNA), 244 µM (PFDA), and 148 µM (PFunDA), confirming that cytotoxicity increases with carbon chain elongation. LFQ-DIA-based proteomics analysis was performed for 100 and 200 µM treatments, quantitatively analyzing approximately 7,000 proteins. Through the analysis of differentially expressed proteins (DEPs), alterations in various mechanisms were discovered; notably, associations with oxidative phosphorylation and thermogenesis-related mechanisms were identified. In conclusion, based on toxicoproteomics, the relative toxicity mechanisms according to PFAS chain length were confirmed.