DIFFERENTIAL-EFFECTS OF HIGH-DOSE GAMMA-IRRADIATION ON THE PRODUCTIONOF TRANSFORMING GROWTH-FACTOR-BETA IN FRESH AND ESTABLISHED HUMAN OVARIAN-CANCER

Tumor Cells from five freshly isolated ovarian tumors and four establi shed human ovarian carcinoma cell lines were analyzed for the producti on of the immunoinhibitory cytokine transforming growth factor-beta (T GF-beta) before and after exposure to gamma irradiation and/or the cyt okines TNF-alpha plus IFN-gamma, All fresh tumors secreted high levels of TGF-beta when compared to the levels produced by the established o varian carcinoma cell lines, TGF-beta produced by fresh tumors was sig nificantly reduced after high doses of gamma irradiation (10,000 cGy), In contrast with the established cell. lines, irradiation significant ly increased TGF-beta secretion, Exposure of fresh tumor cells to cyto kines followed by irradiation caused significant reduction of TGF-beta released when compared to the amount released after exposure to cytok ines only, However, in the established cell lines, cytokines followed by irradiation again significantly increased TGF-beta production, Thes e data indicate that high doses of irradiation in fresh ovarian tumors , unlike established ovarian carcinoma cell lines, can significantly r educe the local production of this potent immunoinhibitory cytokine, T his effect could work to further amplify weak immunological responses within the tumor, In addition, these findings indicate major differenc es between fresh tumor samples and established cell lines and warn aga inst the sole use of continuous cell lines as models for tumors growin g in vivo. (C) 1996 Academic Press, Inc.