The toxicogenomic study on Persistent Organic Pollutants (POPs) in human hepatoma cell line

Abstract

Persistent organic pollutants (POPs) are a major group of contaminants. They are geographically widely distributed, circulate globally, and remain intact in the environment for a long period. POPs accumulate particularly in the fatty tissue of living organisms. Although many chemicals are suspected to have hazardous effects, evaluation of their toxicities remains difficult and challenging. In this study, we used toxicogenomic tools that are simple and economical, as compared to other tools of risk assessment. To predict the risk of environmental toxic substances or compounds, investigation of toxicological mechanisms or biomarkers is important. In this study, we identified hepatotoxicity-related genes induced by three POPs (chlordane, toxaphene, and mirex) in the human hepatocellular carcinoma (HepG2) cell line using microarray and gene ontology (GO) analyses. Using microarray analyses, we identified genes that were up- and down-regulated by greater than 1.5-fold. After the GO analyses, we determined several key pathways that are known to be related to hepatotoxicity, including the metabolism of xenobiotics by apoptosis, complement and coagulation cascades, and cell cycle regulation. Thus, our present study suggests that differentially expressed genes by POPs may provide clues for the hepatotoxic mechanism of POPs. In addition, gene expression profiling by toxicogenomic analyses also affords promising opportunities to reveal new toxicity mechanistic markers.