Effects of Combined Persistant Organic Pollutants on Global Gene Expression in Human HepaRG Cells

The exposure to and contamination by Persistent Organic Pollutants (POPs), which include pesticides used worldwide and polyaromatic hydrocarbons, is detrimental to human health and diverse ecosystems. Although most mechanistic studies have focused on single compounds, living organisms are exposed to multiple environmental xenobiotics, simultaneously, throughout their lives. The experimental evidence useful for assessing the effects of exposure to pollutant mixtures is scarce. We investigated the effects of exposure to a combination of two POPs, which employ different xenosensors, on global gene expression in a human hepatocyte cell model, HepaRG. Whole genome microarrays were used to investigate the effects on the HepaRG transcriptome following exposure to the combination of POPs as compared to each compound individually. Differentiated HepaRG cells were treated with either 2,3,7,8 tetrachlorodibenzo-p-dioxin, alpha-endosulfan (an organochlorine pesticide), the mixture or the DMSO vehicle for 30 hours after which RNA was extracted for hybridization on Affymetrix whole human genome microarrays.