Effects of radiation on TNF alpha-mediated cytolysis of cell lines derived from cervical carcinomas

The effect of radiation, a primary mode of treatment for cervical malignancies, on the tumor necrosis alpha (TNF alpha)-mediated cytolysis of five cell lines derived from human cervical carcinoma cell lines (C-33 A, ME-180, HT-3, MS751, and SiHa) was analyzed. Results of this analysis showed that all of the cell lines were resistant to the cytolytic effects of TNF alpha. Although resistant when protein synthesis proceeds normally, ME-180, HT-3, MS751, and SiHa cells were sensitive to TNF alpha-mediated cytolysis in the presence of protein synthesis inhibitors. The cytolytic response of these cells to radiation was heterogeneous, with C-33 A cells being the most radiosensitive and SiHa cells being the least radiosensitive. The cell lines ME-180, MS751, and HT-3 were intermediate in their sensitivities to radiation. Because radiation is known to inhibit protein synthesis, the ability of radiation to enhance TNF alpha cytolytic activity was examined. The cell lines with intermediate sensitivities to radiation (ME-180, HT-3, and MS751) demonstrated statistically significant synergistic increases in cytolysis when exposed to TNF alpha in combination with radiation. Neither the radioresistant SiHa cell line nor the radiosensitive C-33 A cell line displayed increased cytolysis with increasing concentrations of TNF alpha at any dose of radiation. Possible mechanisms which may explain the synergy in ME-180, HT-3, and MS751 cells and lack of synergy in C-33 A and SiHa cells by TNF alpha and radiation are discussed.