Pesticide mixtures potentiate the toxicity in murine thymocytes

The immunotoxic risks of multiple pesticide exposure were evaluated. C57BL/6 mouse thymocytes were exposed to lindane, malathion, and permethrin, either separately or in mixtures of two pesticides, in vitro. These pesticide exposures caused both apoptotic and necrotic cell death in thymocytes as evaluated by flow cytometric analysis in combination with 7-aminoactinomycin-D (7-AAD), Annexin-V/propidium iodide (PI) staining assays and lactate dehydrogenase release assays. When cells exposed to mixtures of two pesticides, a significantly greater than additive interaction was observed in both apoptotic and necrotic populations of cells. The gel electrophoresis of DNA of cells showed DNA ladder formation with limited genomic DNA and increased laddering in mixture exposures. Based on these findings, it is suggested that these pesticides are potent immunotoxicants, in vitro, and that the mechanism of cytotoxicity observed upon exposure to these pesticides may, at least in part, be due to induction of apoptosis. We also provided evidence that induction of drug metabolizing mixed function oxidase system with lindane may, in part, be responsible for the potentiation of cytotoxicity in the combined exposures. As more information is obtained on the potential immunotoxic effects of pesticides, further insights will be gained for the risk assessment of these environmental pollutants.