The in vitro antiproliferative effects of interferons (IFN) against the human bladder carcinoma cell lines T24, RT4, HT1197, and 647V were evaluated at temperatures ranging from 37–41°. At 37°, the antiproliferative activities of IFN, either naturally produced or produced by recombinant DNA technology, were different against different cell lines. An increase in temperature markedly enhanced the antimitotic effect of IFN for all cells. For example, T24 cells grown at 37° and treated with 200 units naturally produced IFN-α or IFN-β per ml for 7 days were inhibited 50 to 60%. No change in cell proliferation occurred in untreated T24 cells grown at 39.5°. Treatment with 200 units IFN-α or IFN-β per ml at 39.5° inhibited these cells 80 to 90%. Similar results were obtained with IFN produced by recombinant DNA technology and purified to homogeneity. Colony formation by the RT4 cell line, at 37°, was decreased less than 10% with 200 units IFN-α per ml and 63% by 200 units IFN-β per ml. At 39.5°, colony formation by untreated RT4 cells was inhibited 48%. Treatment with IFN-β at 39.5° did not result in an enhancement of the antiproliferative effect; however, treatment with IFN-β enhanced the inhibition from less than 10% to 98%. These results suggest that a supraadditive relationship exists between antiproliferative effects of IFN and temperature elevation. The differences seen between IFN-α and IFN-β may be due to the different stabilities of these two molecules. In order to probe the mechanism of the enhanced antiproliferative effect, activity of an IFN-induced enzyme, 2′-5′-oligoadenylate synthetase, was measured. IFN-α treatment resulted in significantly greater 2′-5′-oligoadenylate synthetase induction at 39.5° than at 37°. Thus, two cellular effects resulting from IFN were augmented by increased temperature.
Supported in part by USPHS Research Grants CA 14520 and CA 27436 from the National Cancer Institute; the latter was obtained through the National Bladder Cancer Project.