Cytokinetic and cytotoxic responses of HeLa cells to the combination of hyperthermia and radiation.
Colony formation and cell cycle changes of HeLa cells were studied after the combination of hyperthermia and 60Co irradiation. Cells were heated by immersion in a water bath. The cell cycle progression was monitored using flow cytometry. The dose survival curve of asynchronous growing cells, with immediate postirradiation thermal treatment at 43 degrees C for 60 min, showed significant enhancement of radiosensitivity. When the sequence of heat and irradiation was varied, the greatest decrease in cell survival was obtained when irradiation was given immediately before or after thermal treatment. Flow cytometry analysis showed that irradiation of exponentially growing cells with 5 Gy induced a G2 block, and that heat treatment immediately after 5 Gy exposure caused a progression delay of the cells from G2 + M to G1 phase. Furthermore, the cellular DNA histogram at 48 hours after 5 Gy exposure, immediately before heating, had more cells in G2 + M phase as compared with cells exposed to 5 Gy alone or thermal treatment at 5 hours before or after 5 Gy exposure. These results suggest that hyperthermia immediately after irradiation inhibits some of the cells accumulated in G2 + M phase from traversing into G1 phase. This inhibition may be related to the synergistic cell-killing by hyperthermia and radiation.