Daunorubicin-resistant Chinese hamster ovary cells expressing multidrug resistance and a cell-surface P-glycoprotein.

Independent lines of Chinese hamster ovary cells resistant to the antineoplastic drug, daunorubicin, were obtained by clonal isolation in increasing drug concentrations. A single daunorubicin-resistant phenotype typified by reduced cellular drug accumulation was observed. These mutants displayed a complex phenotype of resistance to a variety of unrelated drugs. Such properties are similar to those of membrane-altered colchicine-resistant lines (V. Ling and L.H. Thompson, J. Cell. Physiol., 83: 103-116, 1974). Analysis of the plasma membrane components of the daunorubicin-resistant clones by gel electrophoresis revealed a prominent cell surface glycoprotein with a molecular weight of about 170,000. This component was immunologically cross-reactive with the cell surface P-glycoprotein of about the same molecular weight, previously identified in colchicine-resistant cells. Thus, it appears that the mechanism of resistance characterized by P-glycoprotein expression could be the basis of many drug-resistant phenotypes.