Methylglyoxal-bis(guanylhydrazone)-resistant Chinese hamster ovary cells: genetic evidence that more than a single locus controls uptake.

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 Vmax 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 Vmax 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.