PH REGULATION IN SENSITIVE AND MULTIDRUG-RESISTANT EHRLICH ASCITES TUMOR-CELLS

Maintenance and regulation of intracellular pH (pH(i)) was studied in wild-type Ehrlich ascites tumor cells (EHR2) and five progressively da unorubicin-resistant, P-glycoprotein (P-gp)-expressing strains, the ma ximally resistant of which is EHR2/1.3. Steady-state pH(i) was similar in cells expressing different amounts of P-gp, in the absence and pre sence of glucose. In EHR2/1.3, glucose-induced acidification was reduc ed, and proton efflux was increased, compared to the wild-type EHR2, d ifferences which were not caused by increased activity of a Na+/H+ exc hanger in the resistant cells. Comparing all six cell lines, no eviden ce was found for a correlation between the amount of P-gp in the membr ane and pH(i) regulation, which was also unaffected by P-gp modulators . However, a correlation was seen between relative resistance/daunorub icin accumulation and acid extrusion rate, which is likely to be due t o aspects of development of drug resistance other than P-gp.