Synchronous Chinese hamster cells were heated to 45.5°C before, during, or after X-irradiation. The lethal effects of heat and radiation treatment were determined by the capacity of single cells to form colonies. Heat treatment prior to irradiation during G1 or S was more effective, in terms of cell killing than heat treatment during or after irradiation. The time interval between irradiation and subsequent heat treatment influenced survival. The half-time for maximal survival when heat followed irradiation was 20-30 min in both G1 and S phase cells. Survival of cells which were heated, and then irradiated after heat treatment, indicated an independent, additive or synergistic interaction between heat and radiation, depending on the time of heat treatment and the phase of the cell cycle treated. Nine minutes of heat treatment during G1 or 7 min during S decreased the shoulder region and increased the slope of the radiation survival curves. But most important, 7 min of heat prior to irradiation radiosensitized the relatively radioresistant S phase cells more than the relatively radiosensitive G1 cells, and thus virtually eliminated the differences in radiosensitivity normally observed between G1 and S. Repair of heat damage as determined by survival to subsequent irradiation, began approximately 6 hr after 9 min heat treatment during G1, and approximately 12 hr after 7 min heat treatment during S. In both cases, heat damage was repaired in the absence of cell division; for heating in G1, repair occurred during G1, but for heating during S, repair may have been associated with movement into G2. Cells exposed to split heat treatments during S repaired heat damage while they were still in S phase, and maximum survival was attained when 6 hr elapsed between the heat treatments.

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