Murine NIH-3T3 cells were exposed to doxorubicin (DOX, 1 mu g/ml), ethanol (EtOH, 0.2%) and caffeine (CAFF, 200 mu g/ml) and analyzed for the induction of resistance proteins (P-glycoprotein, glutathione S-transferase-pi, catalase) and oncoproteins (c-EOS, c-ERBB1). P-glycoprotein (P-170), glutathione S-transferase-pi (GST-pi) and catalase (CAT) levels were found to be elevated after exposure of the cells to doxorubicin. In EtOH-treated cells the P-170 level was moderately increased (12 to 36 h after exposure), whereas the GST-pi and CAT levels were greatly increased (1 to 48 h). CAFF caused a moderate increase of P-170 (12 to 36 h) and of GST-pi (6 to 72 h). The accumulation of rhodamine 123 was reduced after the level of the resistance proteins had risen. After exposure to DOX, c-FOS was expressed moderately whereas c-ERBB1 was expressed strongly. Both oncoproteins showed a significant increase after exposure to EtOH. Only a moderate increase of c-FOS was seen after exposure to CAFF. Five out of seven additionally investigated rodent cell lines showed an increase in the expression of P-170, GST-pi and c-FOS after exposure to DOX, EtOH or CAFF.

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