Isolation and genetic characterization of dibucaine-resistant variants of a mouse lymphocytic cell line |
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Authors: | Vicki L. Vaughan Joan K. Stadler |
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Affiliation: | Department of Genetics, Iowa State University, Ames, IA 50011, USA |
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Abstract: | A series of dibucaine-resistant (DibR) variants of the mouse lymphoid cell line L5178Y have been induced by mutagen (EMS) and isolated by selection for resistance to a short (48 h), high concentration (0.045 mM) drug pulse. DibR isolates grow exponentially in the presence of 0.025-– 0.030 mM dibucaine, drug concentrations that are toxic to the parent cell line. Like L5178Y, these variants are pseudodiploid. The dibucaine-resistant phenotype has remained stable in four independently derived populations, subcultured for 7 or 11 months in growth medium without drug. Also, the frequency of DibR variants increases as the concentration of inducing mutagen is increased. These latter two findings suggest, but do not prove, that the dibucaine-resistant phenotype occurs because of gene mutation. All DibR isolates were found to be cross-resistant to the growth-inhibiting effects of tetracaine, but sensitive to procaine and benzocaine. Chromosome number or cell size is an important consideration in evaluating the cytotoxicity of dibucaine because normal pseudotetraploid cells are more tolerant to the toxic effects of this drug than are wild-type pseudodiploid cell populations. Hybridization studies indicate that the dibucaine-resistant phenotype of one variant may be dominant, and that of another recessive. DibR variants will be important for future studies of the mechanism of local anesthetic action. |
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