IN-VITRO AND IN-VIVO INDUCTION OF HEAT-SHOCK (STRESS) PROTEIN (HSP) GENE-EXPRESSION BY SELECTED PESTICIDES

The chloroacetamide insecticide alachlor, polyhalogenated cyclic hydro carbons endrin and chlordane and the organophosphate pesticides chlorp yrifos and fenthion induce oxidative tissue damaging effects including lipid peroxidation and nuclear DNA-single strand breaks. The mechanis m involved in the induction of oxidative stress by these xenobiotics i s unknown. No information is available regarding whether these pestici des can induce the expression of heat shock (stress) protein (Hsp) gen es as a common protective mechanism against tissue damage. The pestici des were administered p.o. individually to female Sprague-Dawley rats in two 0.25 LD(50) doses at 0 h and 21 h, The animals were killed at 2 4 h, and liver, brain, heart and lung tissues were removed to examine the induction of Hsps by Western and Northern blot analysis. In a sepa rate series of experiments, cultured neuroactive PC-12 cells were trea ted 24 h with 50, 100 or 200 nM concentrations of these pesticides. Al achlor, endrin, chlorpyrifos and fenthion induced Hsp89 alpha and Hsp8 9 beta in hepatic and brain tissues, as well as in cultured PC-12 cell s. Chlordane induced some expression of Hsp89 alpha but not Hsp89 beta in the hepatic and brain tissues of treated rats. Some expression of Hsp89 beta was observed in lung tissues of endrin and alachlor treated animals. These findings were substantiated by Western blot analysis u sing Hsp90 antibody. Except chlordane all these pesticides induced enh anced synthesis of Hsp90 in cultured PC-12 cells. The results indicate striking tissue differences in the patterns of the Hsps induced by th e pesticides which were used, and demonstrate that these pesticides ca n induce the expression of Hsp89 alpha and Hsp89 beta genes in various target organs of rats. The results support the hypothesis that these genes may be mechanistically involved in protecting tissues against ox idative stress induced by structurally diverse pesticides.