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54- or ßser-Interferon with
-Interferon on Human Cell Lines of Various Histogenesis1
Departments of Human Oncology, Medicine and Surgery, University of Wisconsin Clinical Cancer Center, Madison 53792, and William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705
The antiproliferative effects of human interferon (IFN), IFN-
, IFN-
54, and IFN-ßser, alone and in combination, were assessed on 10 human cell lines. All IFNs were produced by recombinant technology and purified to homogeneity. In all cell lines except one, the addition of IFN-
to either IFN-
54 or IFN-ßser resulted in a synergistic antiproliferative effect, regardless of individual IFN sensitivities or tissue of origin. The only exception was a normal diploid fibroblast cell in which an additive antiproliferative effect occurred with combination IFN treatment. A malignant fibrosarcoma cell line of similar mesenchymal origin demonstrated a synergistic antiproliferative effect. One cell line was sensitive to both type I and type II IFN alone. Three cell lines were relatively resistant to IFN-
but not to IFN-ßser, one was relatively resistant to IFN-ßser but not to IFN-
, and the remainder were resistant to both IFN-
and IFN-ßser or IFN-
54. The addition of IFN-
54 to IFN-ßser in the SKCO 1 cell line resulted in an antagonistic interaction. Timing experiments with RT112 cells indicate that IFN-
and IFN-ßser need not be in the media at the same time for the synergistic effect to occur. Combinations of type I and type II IFN thus resulted in synergistic antiproliferative effect for transformed human cells of various histogenesis, including some with a relative resistance to one or both IFN types.
1 Supported by the Cetus Triton Interferon Program, Grant CA27436 from the National Cancer Institute, the Veterans Administration Research Service, and research funds from the Departments of Surgery and Human Oncology.
2 To whom requests for reprints should be addressed.
Received 9/ 6/84. Revised 5/23/85. Revised 10/24/85. Accepted 10/25/85.
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