We studied the effect of interferon-γ (IFN-γ) and mouse L-cell interferon (IFN-β) on the proliferation of a mouse bladder tumor, MBT-2. A liquid culture clonogenic assay was used, and a linear relationship was obtained between the number of cells plated and the number of colonies formed. When the cells were assayed in the presence of various doses of murine IFN-γ or IFN-β, colony formation was inhibited in a dose-dependent manner. Partially purified IFN-γ was more effective than IFN-β in inhibiting MBT-2 colony formation in that IFN-β exhibited a 50% inhibition dose of approximately 1000 units/ml, while the 50% inhibition dose for the partially purified IFN-γ was approximately 70 units/ml. The 50% inhibition dose for recombinant IFN-γ was 700 units/ml, suggesting that multiple lymphokines were active in the partially purified preparation. Further studies with partially purified IFN-γ showed that the inhibitory effect was time dependent with the maximal effect observed after 48 hr of exposure in a 5-day assay. Treatment of partially purified IFN-γ for 24 hr at pH 2.0 resulted in the abrogation of the antiproliferative effect. Studies in which partially purified IFN-γ preparations were treated with a monoclonal antibody against IFN-γ also resulted in abrogation of antiproliferative activity, confirming the nature of the antiproliferative agent to be IFN-γ. Further studies showed that murine recombinant IFN-γ also inhibited MBT-2 proliferation in a dose-dependent manner, confirming that IFN-γ alone mediates anti-proliferative activity. Combinations of IFN-β and recombinant IFN-γ acted synergistically in the inhibition of MBT-2 proliferation.

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This work was supported by USPHS Grant CA 28860 from the National Cancer Institute through the National Bladder Cancer Project.

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