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Potentiation of the Direct Anticellular Activity of Mouse Interferons: Mutual Synergism and Interferon Concentration Dependence¹

Department of Microbiology, The University of Texas Medical Branch, Galveston, Texas 77550

Mouse immune (IFN-)² and virus-type (IFN-/ß) interferons were used separately and in combination in cloning studies with B-16 melanoma cells. IFN- was found to be a more potent mediator of the direct anticellular effect of interferon than was IFN-/ß, as shown not only by a greater sensitivity of B-16 cells to IFN- but also by a steeper slope of the anticellular sensitivity curve of the IFN-. The differences in the slopes of the curves defining their anticellular effect appeared to be inherent in the interferons themselves and not due to an inhibitor of interferon, a stimulator of cell growth, or another factor possessing anticellular activity. The results are consistent with the interpretation that IFN- and IFN-/ß exert their anticellular effects by different mechanisms. The anticellular activity of interferon against B-16 melanoma replication unit development was potentiated by mixed preparations of IFN- and IFN-/ß. The potentiation appeared to be an expression of a property of the interferons themselves. Replication units resistant to the potentiated activity of the interferons were not detected. Potentiation levels were dependent on the concentrations of both IFN- and IFN-/ß and continued to increase dramatically as the interferon concentrations increased. Maximum potentiation observed was 214-fold at the highest interferon concentrations used. The data suggest that potentiation is a mutual, synergistic interaction of IFN- and IFN-/ß.

¹ Supported by USPHS Grant 5R01 CA 26475 awarded by the Department of Health and Human Services, National Cancer Institute.

Received 8/ 3/81. Accepted 11/30/81.

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