Transforming activities of methotrexate, hydroxyurea and 5-fluorouracil in different cell systems

The transforming ability of methotrexate, hydroxyurea and 5-fluorouracil was studied in mass cultures of embryo cells from BN/a, DBA/2 and Swiss mice. As estimated by virological methods the cells from BN/a mice were infected persistently with ectromelia virus. In parallel a quantitative transformation assay with a cloned BALB/3T3 cell line was employed. Oncogenic transformation could be induced repeatedly in mass cultures from BN/a mice after treatment with every of chemotherapeutic agents studied. Neither of the drugs induced transformation in the cultures deriving from two other strains of mice. In the cloned BALB/3T3 cell line from the three drugs tested only methotrexate induced the appearance of transformed foci, however, the yield of transformants was very low. It has been concluded that under the employed experimental conditions the transforming ability of hydroxyurea and 5-fluorouracil could be expressed exclusively in the cells infected with ectromelia virus. The transforming ability of methotrexate seems to depend either on the presence of viral infection or on the properties of cells enabling additional events necessary for transformation.