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Abstract
<p class="first" id="d9244576e51">Chinese hamster ovary cells selected for resistance
to colchicine display pleiotropic
cross-resistance to a wide range of amphiphilic drugs. The drug-resistant phenotype
is due to a membrane alteration which reduces the rate of drug permeation. Surface
labelling studies reveal that drug-resistant Chinese hamster ovary cell membranes
possess a carbohydrate-containing component of 170 000 daltons apparent molecular
weight which is not observed in wild type cells. Through studies of the metabolic
incorporation of carbohydrate and protein precursors, and through the use of selective
proteolysis, this component is shown to be a cell surface glycoprotein. Since this
glycoprotein appears unique to mutant cells displaying altered drug permeability,
we have designated it the P glycoprotein. The relative amount of surface labelled
P glycoprotein correlates with the degree of drug resistance in a number of independent
mutant and revertant clones. A similar high molecular weight glycoprotein is also
present in drug-resistant mutants from another hamster cell line. Observations on
the molecular basis of pleiotropic drug resistance are interpreted in terms of a model
wherein certain surface glycoproteins control drug permeation by modulating the properties
of hydrophobic membrane regions...
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