Analysis of gene expression changes in relation to hepatotoxicity induced by perfluorinated chemicals in a human hepatoma cell line

Abstract

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) represent a rising class of persistent organic pollutants termed perfluorinated chemicals (PFCs). In this study, hepatotoxic effects of PFCs were examined by microarray and gene ontology (GO) analysis. Human hepatocellular carcinoma (HepG2) cells were exposed to PFOS and PFOA for 48 h, and the RNA was collected. Global gene expression analysis using microarrays revealed 279 and 1,973 genes that changed greater than 1.5-fold after PFOS and PFOA exposure, respectively (P<0.05 for both), with 154 genes common to both PFCs. These genes were enriched in gene ontology (GO) terms and KEGG pathways associated with hepatotoxicity. Many genes were involved in complement and coagulation cascades, PPAR signaling pathway, and regulation of cell proliferation, which coincide with clinical evidence and indicate the critical hepatotoxicity of PFCs. These results show that transcriptome alterations induced by PFOS and PFOA could be possible signatures of the hepatotoxic effects of PFCs.