Multidrug-resistance phenotype in Chinese hamster ovary cells

Cancer Treat Rep. 1983 Oct;67(10):869-74.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Line
  • Colchicine / metabolism
  • Cricetinae
  • Cricetulus
  • Drug Resistance
  • Female
  • Glycoproteins / analysis
  • Membrane Proteins / analysis
  • Mutation
  • Ovary / cytology
  • Phenotype
  • Phytohemagglutinins / pharmacology

Substances

  • Antineoplastic Agents
  • Glycoproteins
  • Membrane Proteins
  • Phytohemagglutinins
  • Colchicine