Altered Drug Permeability in Mammalian Cell Mutants

  • V. Ling
  • S. A. Carlsen
  • Y. P. See
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 84)


The properties of colchicine uptake into Chinese hamster ovary cells were examined and found to be consistent with an unmediated diffusion mode. This uptake was stimulated several fold by metabolic inhibitors. The activation energy of colchicine uptake was found to be 19 kcal per mole; a similar value was obtained in cells stimulated by cyanide. Drug resistant mutants with greatly reduced colchicine permeability have been isolated. They displayed a pleiotropic phenotype, being cross-resistant to a variety of unrelated compounds. The basis of this pleiotropy was due also to reduced drug permeability. Examination of the lipids and fatty acids of parental and mutant cell membranes revealed no major differences. However, a 170,000 dalton surface glycoprotein was observed to be associated with colchicine resistance. This glycoprotein was postulated to be a modulator of drug permeability. All these data are consistent with the concept that mammalian cells are able to regulate the permeation of drugs entering by an unmediated diffusion process.


Chinese Hamster Ovary Cell Mutant Cell Potassium Cyanide Drug Permeability Cell Surface Membrane 


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Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • V. Ling
    • 1
    • 2
  • S. A. Carlsen
    • 1
    • 2
  • Y. P. See
    • 1
    • 2
  1. 1.The Ontario Cancer InstituteUniversity of TorontoTorontoCanada
  2. 2.Department of Medical BiophysicsUniversity of TorontoTorontoCanada

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