Toxicological Impact of Chronic Chlorpyrifos Exposure: DNA Damage and Epigenetic Alterations Induces Neoplastic Transformation of Liver Cells

Organophosphate pesticides (OPPs) are widely used chemical pesticides in all the developed countries. Among the OPPs, Chlorpyrifos (CPF) is predominantly used and has been linked to various adverse health effects from acute to chronic exposure. Exposure to pesticides both occupationally and environmentally causes frequent human health problems including neurological disorders, liver, kidney dysfunctions and cancer. The acute and chronic effects of these environmental toxicants have been linked to epigenetic changes that appear shortly after exposure, but can last for a lifetime and possibly be passed down through generations. The present study investigates the effects of acute and chronic exposure to CPF, the predominantly used OPP globally on human liver cells, focusing on the induction of DNA damage and epigenetic alterations. Human normal liver cells (WRL-68) were acutely and chronically exposed to varying concentrations of CPF. The results revealed significant DNA damage, epigenetic changes and the onset of neoplastic transformation as evidenced by alterations in the DNA repair genes, DNA methyltransferases markers, cell cycle markers, epithelial to mesenchymal transition markers (EMT) and loss of apoptosis. Additionally, chronic CPF exposure led to increased colony formation, proliferation and migratory properties of normal liver cells indicating the neoplastic transformation of these cells. These findings highlight the potential of CPF to disrupt the cellular integrity and promote carcinogenesis in the liver cells. The present study underscores the impact of chronic CPF exposure in the initiation of cancer and also highlights the importance of continued research to fully understand the chronic health implications of CPF, for developing targeted interventions to mitigate its carcinogenic risks.