FUNCTIONAL-STUDIES WITH A FULL-LENGTH P-GLYCOPROTEIN CDNA ENCODED BY THE HAMSTER PGP1 GENE

Hamster cells grown in culture may, like human and mouse cells, develop multidrug resistance (MDR) when exposed to certain cytotoxic chemotherapeutic agents. Several phenotypic features that are characteristic of MDR have been described; these include (1) resistance to many structurally and functionally unrelated drugs that have different cellular targets and modes of action; (2) reversal of MDR by certain agents, including verapamil and cyclosporin A; and (3) reduced intracellular drug accumulation relative to that of drug-sensitive cells. In this report we show that the introduction and overexpression of the hamster pgp1 cDNA confers to otherwise drug-sensitive cells an MDR phenotype with these features. Moreover, pgp1 transfectants showed varying degrees of resistance to anthracycline analogues, indicating that structural analogues of commonly used anticancer agents are capable of circumventing drug resistance conferred by pgp.