Interferon-gamma inhibits cell replication, but not pp60src activity of RSV-transformed fibroblasts.

The present study analyzes the effect of murine IFN-gamma on DNA synthesis, ornithine decarboxylase activity and phosphorylation of pp60src of Rouse sarcoma virus transformed cells. When natural or recombinant IFN-gamma was added to quiescent SR-BALB or L1210 cells, stimulated with fetal calf serum, only the highest IFN-gamma concentrations (2000 U/ml) inhibited DNA synthesis of both tumor lines. By contrast, lower IFN-concentrations (20-200 U/ml) inhibited the DNA synthesis of L1210 but not of SR-BALB tumor cells. A similar pattern of inhibition was observed when ornithine decarboxylase activity was analyzed. Finally, when the levels of phosphorylation in SR-BALB cells were analyzed after IFN-gamma treatment, no difference with untreated controls was observed, even at the highest concentrations. These results suggest that SR-BALB tumor cells are insensitive to IFN-gamma and that src oncogene activity is not affected at IFN-concentrations inhibiting cell growth.