Abstract
Perfluorooctane sulfonate (PFOS) is a persistent environmental pollutant associated with potential hepatoxic effects and other health risks. Despite its widespread distribution, the mechanisms underlying its toxicities remain to be fully understood. To investigate PFOS toxicology, our study utilized HepG2 and THLE-2 human hepatic cell models to replicate conditions reflecting PFOS accumulation in the liver. Cell viability, cell stress, and cell death assays were conducted to assess the toxicological influence of the chemical on both cell lines. Total RNA extraction was performed, followed by cDNA sequencing, and rt-qPCR. The XTT viability assay revealed a dose-dependent decrease in the number of viable cells when incubated with increasing concentrations of PFOS. The inhibitory concentration (IC50) values were approximately 100 micromolar, which led to morphological changes, elevated reactive oxygen species (ROS), and induced early apoptosis in liver cells after 6 h. Based on the transcriptomic analysis for HepG2 cells, mitochondrial genes involved in oxidative phosphorylation were downregulated, including COX, ND, and the ATP synthase family. Additionally, significant alterations of transcripts implicated in cell adhesion molecules (CAMs) were observed. In conclusion, PFOS inhibited cell growth, induced oxidative stress, and elevated apoptotic levels via transcriptomic alteration, including gene transcripts required for mitochondrial activity and cell adhesion.