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Methylglyoxal‐bis(guanylhydrazone)‐resistant Chinese hamster ovary cells: Genetic evidence that more than a single locus controls uptake
Author(s) -
Heaton Mary Anne,
Flintoff Wayne F.
Publication year - 1988
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041360117
Subject(s) - chinese hamster ovary cell , methylglyoxal , biology , phenotype , cell culture , microbiology and biotechnology , efflux , locus (genetics) , somatic cell , hamster , in vitro , drug , genetics , gene , biochemistry , pharmacology , enzyme
Chinese hamster ovary cells spontaneously resistant to the cytotoxic action of methylglyoxal‐bis(guanylhydrazone) have been isolated in a multistep selection scheme. A low‐level resistant isolate has been shown to be defective in the ability to accumulate the drug intracellularly. This was reflected in a 10‐fold lower V max than wild‐type cells for drug uptake as well as a slight enhancement of drug efflux. More highly resistant isolates selected from this low‐level resistant isolate were totally deficient in the ability to take up the drug. A partial revertant, selected from this low‐level resistant isolate, retained some change in the V max for uptake but lost the accelerated rate of efflux characteristic of the low‐level resistant line. Genetic analysis by somatic cell hybridization indicated that the low‐level resistant phenotype was recessive to the wild‐type phenotype. In addition, the low‐level resistant phenotype could be complemented by a previously isolated highly resistant cell also defective in drug uptake (Mandel and Flintoff 1978) J. Cell. Physiol., 97: 335–344). Taken together, these data suggest that more than one locus controls drug uptake in Chinese hamster ovary cells.