Influence of thermotolerance on the interaction between hyperthermia and radiation in a solid tumourin vivo

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Abstract
The influence of thermotolerance (a temporary resistance to a subsequent heat treatment induced by prior heating) on the response of a C3H mouse mammary carcinoma to combined water-bath hyperthermia and radiation was investigated. Prior heating at 43.5.degree. C for 30 min induced thermotolerance which was at a maximum 16 h later and had completely disappeared after 120 h. Prior heating reduced tumor response to simultaneous heat and radiation given 16 h later, as evidenced by a reduction from 5.1 to 3.3 in the thermal enhancement ratio (TER). The effect was lost by 120 h. Development of thermotolerance apparently reduces the degree of thermal radiosensitization. However, although the time course was the same, the prior heating effect on the combined treatment was smaller than on the resistance to heat alone. With sequential treatment, the tumors were treated with X-rays (28 Gy [gray]) followed 4 h later by 2 dose heat treatment at 43.5.degree. C, the 1st for 30 min and the 2nd after an interval of 0, 16 or 120 h. With this treatment thermotolerance fully manifested itself. It was necessary to increase the duration of heating when applied 16 h after prior heating by a factor of 5.4 to cause a TR of 2.0, a value not significantly different from the expected value of 5.2, i.e., the thermotolerance ratio for heat alone.