CYP1/2 Activation and Glutathione-dependent Cytotoxicity of Four Pesticides in Hep G2 and Fa32 Cells

The cytotoxicity of the carbamate insecticide carbaryl, the organophosphate insecticide quinalphos, the benzimidazole fungicide benomyl, and its debutylcarbamoylated derivative carbendazim was investigated in rat (Fa32) and human (Hep G2) hepatoma-derived established cell lines. Benomyl was the most toxic of the four pesticides, followed by quinalphos, carbaryl and the least toxic carbendazim, suggesting that the butylcarbamoyl group plays an important role in the toxicity of benomyl. EROD (7-ethoxyresorufin-O-deethylase) and PROD (7-pentoxyresorufin-O-depentylase) activity were moderately activated in Fa32 cells. In Hep G2 cells no PROD was measured, but EROD was activated 2.5 to 28 times the control values. Piperonyl butoxide and 1-aminobenzotriazole did not influence the cytotoxicity of the pesticides. However, when the endogenous glutathione content was reduced by pretreatment of the cells with l-buthionine-S,R-sulfoximine, the cytotoxicity of the pesticides strongly increased in both cell lines. In conclusion, the same cytotoxicity was observed for the four pesticides in both the animal and the human cell line. CYP1/2-dependent enzymes were activated to different degrees. No evidence was obtained for a cytochrome P450-dependent cytotoxicity, but glutathione showed a protective effect against the four pesticides in both cell lines.