Antiproliferative and recovery effects during treatment of breast and ovarian carcinoma cell cultures with interferon-gamma.

Abstract

We studied the antiproliferative effects of human interferon-gamma (IFN-gamma) on cell lines derived from human carcinomas (three breast, two ovarian, and one renal) and recovery from these effects when IFN-gamma was removed after 6 or 72 h. IFN-gamma led to a dose-dependent and time-dependent cytostatic inhibition of all six tumor cell lines; the renal carcinoma cells were by far the most sensitive, and with these, cytotoxic effects were also seen. The 50% inhibitory dose (ID50) for each cell line was different and remarkably constant over many months. When cells were exposed to IFN-gamma for only 9 or 72 h, those from three lines recovered completely from the growth inhibitory effects, but from three only partially. When cultured for several weeks in the presence of 1600 U/ml of IFN-gamma, two lines developed increased resistance to IFN-gamma, one became much less sensitive, and two showed no changes in sensitivity. We saw no correlations between these changes during continuous exposure to IFN-gamma and the antiproliferative ID50 for each cell or whether the cells recovered completely from the inhibitory effects of IFN-gamma after short-term exposure. Nevertheless, cells with a population doubling time of less than 48 h had low to moderate sensitivity to IFN-gamma and seemed to recover more completely than those doubling in more than 61 h. Our results indicate great individual variation in the in vitro sensitivity of carcinoma cells to the antiproliferative effects of IFN-gamma.