Interaction of Hyperthermia and Radiation on the Survival of Synchronous 9L Cells

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Abstract
The response of cultured 9L rat brain tumor cells to hyperthermia (45.degree. C water bath) and ionizing radiation was investigated as a function of their position in the cell cycle. Similar to other cell lines, 9L cells demonstrated a sensitivity to cell killing by hyperthermia during S phase, and in particular late S phase, in contrast to high survival in early G1 phase. Mitotic cells treated prior to selection under proper pH and temperature conditions displayed a survival that was comparable to that of S-phase cells. Using the method of retroactive synchrony, the thermal sensitivity during mitosis also fluctuated, being greater for cells closer to division than those near the G2/M boundary. Irradiated 9L cells exhibit only minimal changes in survival across the majority of the cell cycle (except for a radiosensitive mitosis). Combining the 2 agents resulted in survival levels that were less than expected from the product of the survivals after individual treatments. The degree of enhancement was greatest for those cells in mid-G1 phase and S phase. When the 2 treatments were separated in time, there was an increase in survival that was greater when X-rays preceded heat than for the reverse sequence. The degree of recovery was greater for cells initially treated at the S/G2 boundary, than at the G1/S boundary, than at mid-G1. Recovery to an independent level was reached within 1 h for all positions except mid-G1 when radiation preceded hyperthermia; for the reverse sequence, recovery to an independent level was not observed over a 4 h period.