The isolation and initial characterization of dibucaine-resistant variants of a mouse lymphocytic cell line
A series of dibucaine-resistant variants (Dib('R)) of the mouse lymphoid cell line L5178Y were isolated after treatment with the mutagen ethyl methane sulfonate and exposure to a high concentration of the local anesthetic dibucaine (0.045 mM) for 48 hours. The Dib('R) isolates demonstrate exponential growth in the presence of 0.025 mM to 0.030 mM dibucaine, drug concentrations that are toxic to the parent cell line. When cultured in the absence of the drug, the variants display a stable transmission of the dibucaine-resistant phenotype, and the frequency of Dib('R) 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 Dib('R) isolates were found to be cross resistant to the growth-inhibiting effects of tetracaine, a second local anesthetic. However, in the presence of the local anesthetics procaine and benzocaine, the variants were as growth limited as the parental line.;Chromosome number of cell size is an important consideration when evaluating the toxicity of this drug because normal pseudotetrapoloid cells are more tolerant to the toxic effects of dibucaine than are wild type pseudodiploid cell populations. Hybridization studies indicate that the dibucaine-resistant phenotype of one variant may be genetically recessive, and variant line may be completely dominant when compared with the corresponding pseudotetraploid variant control.