Thermotolerance after fractionated hyperthermia: assessment of cell survival by response to X-rays

A previous study of the mouse ear showed that daily treatment at 43.5 degrees C, either 10 X 20 min or 20 min + 9 X 70 min, induced the same resistance to further heating as was induced by a single treatment of 20 min. The results could be explained in at least two ways: (a) no cells are killed by the heat treatments but thermotolerance is induced; and (b) a proportion of cells is killed by each fraction and the degree of thermotolerance induced in survivors increases as the number of fractions is increased. These two possibilities were tested by measuring the response to X-rays at 24 h after various regimes of fractionated hyperthermia. At this time interval the enhancing effect of a single heat treatment would have decayed, so that radiosensitivity should then be related to the number of surviving cells. Up to 49 daily treatments of 20 min had little effect on radiosensitivity, suggesting that these heating regimes did not cause a significant reduction in the number of basal epidermal cells. A regime of 20 min + 4 X 70 min daily also had little effect but a treatment of 20 min + 9 X 70 min daily increased the radiation response, suggesting that the more severe heat treatment had reduced cell survival to approximately 4 per cent.