Multidrug-resistance phenotype in Chinese hamster ovary cells.
Multidrug resistance is a complex pleiotropic phenotype of cross-resistance and collateral sensitivity to unrelated compounds observed in many mammalian cell mutants selected for resistance to single agents. In Chinese hamster ovary cells, colchicine-resistant mutants expressing this phenotype have been characterized extensively. Such mutants arise apparently from a single genetic event, and the basis of this phenotype appears to be localized at the membrane level, resulting in altered drug permeability. Expression of a 170,000-dalton surface glycoprotein (P-glycoprotein) has been identified to correlate with the multidrug-resistance phenotype. Selection of a second mutation in colchicine-resistant mutants, for resistance to phytohemagglutinin, results in an alteration of the carbohydrate moiety in P-glycoprotein and other surface components. This mutation does not noticeably affect the multi-drug-resistance phenotype. The altered permeability of mutant cells to drugs, however, can be modulated by nonionic detergents or metabolic inhibitors. These findings are consistent with a molecular mechanism of multidrug resistance whereby the pleiotropic response of the cell is mediated by an overexpression of a cell-surface protein, the P-glycoprotein.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D003078:Colchicine / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004351:Drug Resistance; D005260:Female; D006023:Glycoproteins / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D009154:Mutation; D010053:Ovary / Q000166:cytology; D010641:Phenotype; D010835:Phytohemagglutinins / Q000494:pharmacology
D000970:Antineoplastic Agents; D006023:Glycoproteins; D008565:Membrane Proteins; D010835:Phytohemagglutinins; D003078:Colchicine