Cellular impact of combinations of endosulfan, atrazine, and chlorpyrifos on human primary hepatocytes and HepaRG cells after short and chronic exposures

摘要: Chronic exposure to low doses of pesticides present in the environment is increasingly suspected cause major health issues humans. Toxicological evaluations become more complex when concerns chemical combinations. Atrazine, chlorpyrifos, and endosulfan are used worldwide agriculture therefore currently found at residual levels food environment, even countries which they now banned. Our study aimed use Real-Time Cell Impedance Analyzer investigate changes phenotypical status primary human hepatocytes differentiated HepaRG cells induced by short chronic exposures these three chemicals. In contrast traditionally endpoint cytotoxicity test, this technology allows kinetic measurements real-time throughout entire experiment. data show significantly higher cytotoxic effects mixtures as compared individual a greater susceptibility short-term (24 h). Repeated over 2 weeks endosulfan-containing mixture cell death time- dose-dependent manner. Of typical genes involved metabolism cell-response xenobiotics, we an condition-dependent deregulation expression CYP3A4 UGT1A exposed mixtures. demonstrate usefulness monitoring long-term toxicological co-exposure xenobiotics. addition, support but same time highlight certain limitations gold standard liver model toxicity studies.