The prevalence of ouabain-resistant variants after mutagen treatment. Lack of correlation between the frequency of variant expression and the metastatic phenotype.

In order to test the hypothesis that tumor cells with greater malignant potential should have an increased sensitivity to mutagens, four individual murine cell lines, each paired for their metastatic and nonmetastatic potentials, were compared with respect to the prevalence at which ouabain-resistant mutants could be obtained after treatment of the cells with the mutagen MNNG. No increase in the prevalence of induced mutation in metastatic cells was observed; and, in fact, in two cases (h-ras-transfected 3T3 and SP1 cells), nonmetastatic cells had a higher prevalence of mutations after MNNG treatment than did their metastatic counterparts. We suggest that the absolute level of genomic instability, measured by this means, is not critical to malignant potential and tumor progression.