BACKGROUND: This investigation, which evaluates the combination of radiation and interferon, bridges two clinical treatments of cancer. Radiation therapy (RT) is an integral part of cervical cancer treatment; interferons (IFN), however, are classified as modifiers of biologic response. The authors evaluated the radiation-modulation effects of recombinant alpha-IFN and beta-IFN on two different human cervical cancer cell lines: ME-180 and SiHa. The radiation sensitivity based on the cell growth rate (logarithmic growth phase versus confluence) was also evaluated. METHODS: Control cells and cells pretreated with either alpha-IFN or beta-IFN were exposed to RT at doses of 0, 2, 5, 10, and 15 Gy. The pretreated cells received IFN at doses of 100, 500, 1000 and 5000 IU/ml for 24 hours. The adenosine triphosphate bioluminescence assay was used to measure the surviving fractions after 7 days of incubation. The data were analyzed using the linear-quadratic model and the radiosensitivity index D. The combined effects of IFN and RT on cytotoxicity were evaluated using the synergistic interaction formula for anticancer agents. RESULTS: The ME-180 and SiHa cell lines had the same mean inactivation D values of 13.2 when radiated at confluence. Irradiation of ME-180 and SiHa cells in the logarithmic growth phase resulted in mean inactivation D values of 7.5 and 10.2, respectively. Enhanced radiosensitivity was observed in all IFN-RT combinations. Synergism was observed in the majority of experiments. CONCLUSIONS: Recombinant alpha-IFN and beta-IFN potentiate the radiotoxicity of two cervical cancer cell lines. ME-180 cells were less sensitive to IFN alone than were SiHa cells, but they showed higher a radiosensitizing effect from both IFN. Proliferating cells were more sensitive than confluent cells to RT by itself and to RT-IFN combinations.
BACKGROUND: This investigation, which evaluates the combination of radiation and interferon, bridges two clinical treatments of cancer. Radiation therapy (RT) is an integral part of cervical cancer treatment; interferons (IFN), however, are classified as modifiers of biologic response. The authors evaluated the radiation-modulation effects of recombinant alpha-IFN and beta-IFN on two different human cervical cancer cell lines: ME-180 and SiHa. The radiation sensitivity based on the cell growth rate (logarithmic growth phase versus confluence) was also evaluated. METHODS: Control cells and cells pretreated with either alpha-IFN or beta-IFN were exposed to RT at doses of 0, 2, 5, 10, and 15 Gy. The pretreated cells received IFN at doses of 100, 500, 1000 and 5000 IU/ml for 24 hours. The adenosine triphosphate bioluminescence assay was used to measure the surviving fractions after 7 days of incubation. The data were analyzed using the linear-quadratic model and the radiosensitivity index D. The combined effects of IFN and RT on cytotoxicity were evaluated using the synergistic interaction formula for anticancer agents. RESULTS: The ME-180 and SiHa cell lines had the same mean inactivation D values of 13.2 when radiated at confluence. Irradiation of ME-180 and SiHa cells in the logarithmic growth phase resulted in mean inactivation D values of 7.5 and 10.2, respectively. Enhanced radiosensitivity was observed in all IFN-RT combinations. Synergism was observed in the majority of experiments. CONCLUSIONS: Recombinant alpha-IFN and beta-IFN potentiate the radiotoxicity of two cervical cancer cell lines. ME-180 cells were less sensitive to IFN alone than were SiHa cells, but they showed higher a radiosensitizing effect from both IFN. Proliferating cells were more sensitive than confluent cells to RT by itself and to RT-IFN combinations.