CHEMORESISTANCE TO DOXORUBICIN AND CISPLATIN IN A MURINE CELL-LINE - ANALYSIS OF P-GLYCOPROTEIN, TOPOISOMERASE-II ACTIVITY, GLUTATHIONE ANDRELATED ENZYMES

Resistance to antineoplastic drugs has often been associated with P-gl ycoprotein overexpression, this certainly being not the sole mechanism . In order to characterize resistance to doxorubicin and cisplatin, we have analysed P-glycoprotein expression, topoisomerase II activity, g lutathione and related enzymes in murine leukemic cells (doxorubicin o r cisplatin-resistant). The doxorubicin-resistant cells contained P-gl ycoprotein, showed lower activities fo glutathione S-transferase well as of glutathione reductase and topoisomerase II. The modifications ob served in the most cisplatin-resistant cell line were a higher activit y of glutathione S-transferase isoenzyme pi and topoisomerase II. Thes e results suggest that drug uptake, glutathione metabolism as well as topoisomerase II activity are all characteristic of multidrug resistan ce.