INDUCTION OF P-GLYCOPROTEIN, GLUTATHIONE-S-TRANSFERASE-PI, CATALASE, C-FOS AND C-ERBB1 IN RODENT CELL-LINES AFTER EXPOSURE TO DOXORUBICIN, ETHANOL AND CAFFEINE

Murine NIH-3T3 cells were exposed to doxorubicin (DOX, 1 mu g/ml), eth anol (EtOH, 0.2%) and caffeine (CAFF, 200 mu g/ml) and analyzed for th e induction of resistance proteins (P-glycoprotein, glutathione S-tran sferase-pi, catalase) and oncoproteins (c-EOS, c-ERBB1). P-glycoprotei n (P-170), glutathione S-transferase-pi (GST-pi) and catalase (CAT) le vels were found to be elevated after exposure of the cells to doxorubi cin. In EtOH-treated cells the P-170 level was moderately increased (1 2 to 36 h after exposure), whereas the GST-pi and CAT levels were grea tly increased (1 to 48 h). CAFF caused a moderate increase of P-170 (1 2 to 36 h) and of GST-pi (6 to 72 h). The accumulation of rhodamine 12 3 was reduced after the level of the resistance proteins had risen. Af ter exposure to DOX, c-FOS was expressed moderately whereas c-ERBB1 wa s expressed strongly. Both oncoproteins showed a significant increase after exposure to EtOH. Only a moderate increase of c-FOS was seen aft er exposure to CAFF. Five out of seven additionally investigated roden t cell lines showed an increase in the expression of P-170, GST-pi and c-FOS after exposure to DOX, EtOH or CAFF.