COMPARATIVE IN-VITRO AND IN-VIVO PROTEIN-KINASE-C ACTIVATION BY SELECTED PESTICIDES AND TRANSITION-METAL SALTS

Various pesticides and transition metals induce oxidative deterioratio n of biological macromolecules. Protein kinase C (PKC) may mediate the se effects. However, no information is available regarding whether the se xenobiotics can modulate PKC which is a critical event signaling th e increase in endothelial permeability and cell proliferation. Female Sprague-Dawley rats were treated p.o. with two 0.25 LD(50) doses of se lected pesticides and transition metal salts at 0 and 21 h, and killed at 24 h. PKC activities were measured in liver and brain tissues. Cul tured PC-12 cells were incubated for 24 h with 50, 100 or 200 nM conce ntrations of these pesticides, while 0.20, 0.40 or 0.60 mu M concentra tions of cadmium chloride (Cd(II)) and sodium dichromate (Cr(VI)) salt s were employed. PKC activations were observed in the hepatic and brai n cytosol fractions by all xenobiotics. Approximately 1.4- to 2.0-fold and 1.6- to 3.5-fold increases in PKC activity in the hepatic and bra in cytosol fractions were observed, respectively. In the hepatic tissu es, the greatest increases in activities were observed with TCDD, chlo rpyrifos, endrin and Cd(II), while chlorpyrifos and fenthion exerted t he greatest increases in the brain tissues. In cultured PC-12 cells, t he greatest activation of PKC was observed primarily with 100-nM conce ntrations of the pesticides. The maximum effects were induced by chlor pyrifos, fenthion, Cd(II) and Cr(VI) salt. The results clearly indicat e that pesticides as well as Cd(II) and Cr(VI) salts can modulate a vi tal component of the cell signaling pathway, namely PKC activity. PKC may be a target of free radicals and oxidative stress, leading to alte red cell proliferation and differentiation. (C) 1997 Elsevier Science Ireland Ltd.