Diazinon cytotoxicity and transfer in Caco-2 cells: Effect of long-term exposure to the pesticide.

ABSTRACT

The purpose of this work was to investigate the effect of prolonged exposure to diazinon (widely used organophosphorus pesticide) on the intestinal cell-line Caco-2. Cytotoxicity of the pesticide (50µM-6mM) significantly decreased in long-term exposed (20µM, 2 months) cells, compared to untreated control cells. In long-term exposed cells, the resistance to diazinon cytotoxicity was reversed in the presence of PSC-833, a P-glycoprotein (P-gp) inhibitor, but not in the presence of MK 571, a Multidrug Resistance Protein (MRP) inhibitor. Cell exposure to 25µM diazinon showed a secretory-directed transport of the molecule, which increased in long-term exposed cells. This efflux decreased significantly, for both long-term and non-exposed cells, in the presence of verapamil and PSC-833, but not MK 571. Furthermore, the total amount of P-gp increased in long-term exposed cells. These results suggest that ABC transporter P-gp is involved in the intestinal transfer of diazinon, and that repeated exposure to low doses of diazinon could strengthen the activity of ABC transporters in intestinal cells, thus increasing cell resistance to pesticide cytotoxicity.