Insecticide cytotoxicity and CYP1A1/2 induction in primary human and rat hepatocyte cultures

With the increasing demand for insecticide products, the question of their safety has become one of the serious world public health concerns. The capability of compounds belonging to the major insecticide families [such as chlorinated hydrocarbons (DDT), carbamates (carbaryl: CBR), organophosphorus compounds (malathion, tetrachlorvinfos: MAL, TCV), pyrethroids (cypermethrin: CPR) and benzoylurea (diflubenzuron: DFU)] in inducing CYP1 Al in rat and human hepatocyte cultures has been tested. Cells were treated during 3 days with six non-toxic increasing doses of insecticides and CYP1A1 expression was assessed by ethoxyresorufin O-deethylase (EROD) activity and by Northern blots. A strong and dose-dependent induction was observed with TCV and DFU, both in human (approx. five- and sevenfold over control, respectively) and in rat hepatocytes (approx. sevenfold). However, EROD induction and CYP/A1 mRNA levels were correlated for DFU but not for TCV, suggesting different regulation mechanisms for PCYP1A1 gene expression by the two compounds. CBR and CPR exerted less induction in both cell types (approx. 2.5-fold induction compared with approximately 16-fold for 3-methylcholanthrene), whereas DDT and MAL showed no action on human hepatocytes but decreased EROD activity in rat cells. Finally, cytotoxicity studies performed using the MTT and the neutral red tests demonstrated significant differences between insecticides.