INHIBITION OF MOUSE BLADDER-TUMOR PROLIFERATION BY MURINE INTERFERON-GAMMA AND ITS SYNERGISM WITH INTERFERON-BETA

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (10) , 4377-4381
Abstract
The effect of interferon-.gamma. (IFN-.gamma.) and mouse L-cell interferon (IFN-.beta.) on the proliferation of a mouse bladder tumor, MBT-2 was studied. A liquid culture clonogenic assay was used and a linear relationship was obtained between the number of cells plated and the number of clonies formed. When the cells were assayed in the presence of various doses of murine IFN-.gamma. or IFN-.beta., colony formation was inhibited in a dose-dependent manner. Partially purified IFN-.gamma. was more effective than IFN-.beta. in inhibiting MBT-2 colony formation in that IFN-.beta. exhibited a 50% inhibition dose of .apprx. 1000 U/ml, while the 50% inhibition dose for the partially purified IFN-.gamma. was .apprx. 70 U/ml. The 50% inhibition dose for recombinant IFN-.gamma. was 700 U/ml, suggesting that multiple lymphokines were active in the partially purified preparation. Further studies with partially purified IFN-.gamma. showed that the inhibitory effect was time dependent with the maximal effect observed after 48 h of exposure in a 5-day assay. Treatment of partially purified IFN-.gamma. for 24 h at pH 2.0 resulted in the abrogation of the antiproliferative effect. Studies in which partially purified IFN-.gamma. preparations were treated with a monoclonal antibody against IFN-.gamma. also resulted in abrogation of antiproliferative activity, confirming the nature of the antiproliferative agent to be IFN-.gamma.. Further studies showed that murine recombinant IFN-.gamma. also inhibited MBT-2 proliferation in a dose-dependent manner, confirming that IFN-.gamma. alone mediates antiproliferative activity. Combinations of IFN-.beta. and recombinant IFN-.gamma. acted synergistically in the inhibition of MBT-2 proliferation.