Studies on revertant cells resistant to transformation by the ras gene family have been extended. Studies with the electron probe have indicated that, in every case examined, ras-transformed cells exhibit specific differences in monovalent cation transport when compared to control NIH/3T3 cells: Upon incubation in medium with lmM ouabain or in medium lacking potassium, the loss of potassium is significantly higher in ras-transformed cells than in controls. This change most likely is responsible for the dramatically increased sensitivity of a ras-transformed cells to ouabain previously reported. Revertant cells, which contain active ras genes but are resistant to retransformation by the ras, src, and fes oncogenes, have altered phenotypes such that the loss of potassium is much less rapid. After studying the transport of potassium in 3 different revertants, we have concluded that at least 2 different mechanisms exist for generating the revertant phenotype from ras-transformed cells. Since both mechanisms result in changes in monovalent cation transport, it seems likely that this change is critical for the maintenance of the transformed phenotype. Ouabain sensitivity of control and ras-transformed cell lines have been extended to human cells, where transformation by the ras oncogene also renders cells more susceptible to ouabain. Ouabain toxicity in human cells is pH dependent. pH effects have not been observed in mouse cells.
