Determination of in vitro hepatotoxic potencies of a series of perfluoroalkyl substances (PFASs) based on gene expression changes in HepaRG liver cells

• DOI: 10.1007/s00204-023-03450-2
• Publication Date: 2023-03-03T03:02:50Z
• Authors: Jochem Louisse; Styliani Fragki; Deborah Rijkers; Aafke Janssen; Bas van Dijk; Liz Leenders; Martijn Staats; Bas Bokkers; Marco Zeilmaker; Aldert Piersma; Mirjam Luijten; Ron Hoogenboom; Ad Peijnenburg
• Keywords: HBM4EU; Fluorocarbons; Drug-Related Side Effects and Adverse Reactions; Gene Expression; Organ Toxicity and Mechanisms; Rats; Relative potency; Alkanesulfonic Acids; Liver; PFASs; HepaRG cells; Hepatocytes; Humans; Animals; Transcriptomics

Abstract Per- and polyfluoroalkyl substances (PFASs) are omnipresent have been shown to induce a wide range of adverse health effects, including hepatotoxicity, developmental toxicity, immunotoxicity. The aim the present work was assess whether human HepaRG liver cells can be used obtain insight into differences in hepatotoxic potencies series PFASs. Therefore, effects 18 PFASs on cellular triglyceride accumulation (AdipoRed assay) gene expression (DNA microarray for PFOS RT-qPCR all PFASs) were studied cells. BMDExpress analysis data indicated that various processes affected at level. From these data, ten genes selected concentration–effect relationship using analysis. AdipoRed derivation vitro relative PROAST In potency factors (RPFs) could obtained 8 (including index chemical PFOA) based whereas genes, RPFs 11–18 PFOA). For readout OAT5 expression, found correlate general well with each other (Spearman correlation) except PPAR target ANGPTL4 PDK4 . Comparison from vivo studies rats indicate best correlations CXCL10 changes external RPFs. HFPO-TA most potent PFAS tested, being around tenfold more than PFOA. Altogether, it may concluded model provide relevant which regarding their applied as screening tool prioritize further hazard risk assessment.