Dose-response analysis of the effects of persistent organic pollutants (POPs) on gene expression in human hepatocytes

Abstract

Determination of gene expression profile alterations following dose-dependent exposure to toxicants will greatly improve the utility of arrays in identifying biomarkers and elucidating modes of toxicity. In the present study, the effects of increasing doses of persistent organic pollutants (POPs) on the expression of toxicity-related genes were evaluated. Human hepatocellular carcinoma (HepG2) cells were exposed to nontoxic (NT) and 20% inhibitory concentrations (IC20) of the well-known toxic PoP compounds, toxaphene (TOX) and chlordane (CD), for 48 h. Transcriptomic profiling showed differential gene expression patterns and a profound effect on gene expression changes in the IC20 exposure group. Through clustering analysis, 98 NT- and 336 IC20-specific genes and 73 genes expressed dose-dependently were identified. Gene Ontology (GO) analysis identified several key pathways related to the adverse health effects of POPs. In conclusion, this report describes changes in gene expression profiles in hepatocytes in response to different doses of POPs and relates these changes to hepatotoxicity-related pathways. Moreover, novel genes and pathways that may potentially play a role in the prevention of liver disease due to POP exposure were identified.