ATPASE ACTIVITY OF P-GLYCOPROTEIN RELATED TO EMERGENCE OF DRUG-RESISTANCE IN EHRLICH ASCITES TUMOR-CELL LINES

We have characterized the ATPase activity of a sensitive and five prog ressively daunorubicin resistant Ehrlich ascites tumor cell lines pass aged in mice. For the nine different modulators of drug resistance tha t we have studied, the ATPase activity first rose with the modulator c oncentration and then declined. We analyzed the ATPase activity profil es in terms of an activation constant and an inhibition constant for e ach of the nine drugs and six cell lines. In this series of cell lines , the drug-stimulatable ATPase activity was directly proportional to t he amount of P-glycoprotein. Pumping of daunorubicin was also correlat ed with the amount of P-glycoprotein, except that, for a highly passag ed line more daunorubicin was pumped than could be accounted for by th e content of P-glycoprotein. Between the 12th and the 36th passage an additional source of resistance emerged, which was not correlated with P-glycoprotein. Pumping of daunorubicin was negatively correlated wit h the cell volume for the different lines. (C) 1997 Elsevier Science B .V.