Rates of generation of methotrexate-resistant variants in cells temperature-sensitive for malignant transformation.

We used tsLA23-NRK cells, in which malignant transformation is under the control of a temperature-sensitive (ts) src oncogene, to examine the relationship between genetic instability and malignant transformation. Cells were maintained in vitro as either transformed cells (at 36 degrees C) or as normal cells (at 39 degrees C). Genetic instability was assessed in these two cell populations by determining (1) the frequencies of methotrexate (MTX)-resistant variants present in these populations, and (2) the rates of generation of MTX-resistant variants, as determined from Luria-Delbrück fluctuation analyses. We observed no significant differences, in either of these parameters of genetic instability, that could be attributed to transformation status. We conclude that in this defined cellular system there is no obligatory relationship between malignant transformation and increased genetic instability, as assessed by either frequencies or rates of generation of variants resistant to MTX.