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Time-dependent differential effects of natural and recombinant murine interferon-gamma on ornithine decarboxylase activity of tumor cells.

Incubation of quiescent tumor cells with fetal calf serum induced ornithine decarboxylase (ODCase) activity concomitantly with mitogenic stimulation. Pretreatment of cells with highly purified natural or recombinant murine interferon-gamma (MuIFN-gamma) for 5 h caused a dose-dependent increase of ODCase activity induced by fetal calf serum (FCS). Pretreatment of target cells with IFN-gamma for 5 h in absence of FCS stimulation did not induce ODCase activity. When pretreatment of cells with natural or recombinant MuIFN-gamma was prolonged for 18 h both ODCase activity and DNA synthesis induced by FCS were suppressed. By contrast when a mixture of MuIFN-alpha and -beta was used, ODCase activity was significantly suppressed after 5 h pretreatment compared to untreated controls. These results suggest that IFN-gamma exerts a differential effect on mitogen-stimulated events depending on the dose and the time of addition.