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Daunorubicin-resistant Chinese Hamster Ovary Cells Expressing Multidrug Resistance and a Cell-Surface P-Glycoprotein¹

Ontario Cancer Institute, Princess Margaret Hospital and Department of Medical Biophysics, University of Toronto, Toronto M4X 1K9 [N. K., M. S., V. L.], and Research Institute, The Hospital for Sick Children and Departments of Biochemistry and Clinical Biochemistry, University of Toronto, Toronto M5G 1X8 [J. R. R.], Ontario, Canada

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.

¹ Research was supported by the National Cancer Institute of Canada and by the Medical Research Council of Canada.

² To whom requests for reprints should be addressed.

³ Present address: Banting and Best Department of Medical Research, University of Toronto, Toronto, Canada M5G 1L6.

Received 12/16/82. Accepted 6/10/83.

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