Abstract

The effect of step-down heating (SDH) on the interaction between heat and radiation was investigated in a C3H mammary carcinoma in vivo. SDH consisted of an initial sensitizing treatment (ST) performed at 44.5 degrees C or 43.5 degrees C followed by a lower temperature test treatment (TT) in the range 41.0-43.0 degrees C. Step-up heating (SUH), i.e. TT followed by ST, and single heating were used as controls. The end-point was the radiation dose needed to control 50% of the tumours (TCD50). The results were evaluated by calculating the thermal enhancement ratio (TER) defined as TER = TCD50 (radiation alone)/TCD50 (radiation and heat). For a simultaneous application of TT and radiation a significant enhancement of direct heat radiosensitization was observed with increasing ST time or ST temperature using SDH. In contrast, only a minor increase was seen with SUH. A comparison between TCD50 values for the corresponding SUH and SDH schedules revealed that the SDH effect was largest at 41.0-42.0 degrees C and decreased with increasing TT temperature. The radiosensitizing effect of SDH also decreased if an interval was allowed between ST and TT or between TT and radiation. However, as a result of an increased cytotoxicity towards hypoxic tumour cells, the TCD50 value for SDH remained significantly smaller than for SUH, even with a sequential combination of radiation and heat.

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