Time-temperature relationships for hyperthermal radiosensitisation in mouse intestine: influence of thermotolerance.

Thermal enhancement of radiation injury to the crypt compartment of mouse small intestinal mucosa has been measured as a function of heating time for temperatures in the range 41.0-44.0 degrees C. All the hyperthermal treatments used were themselves subthreshold for gross tissue injury. With this limitation, thermoradiosensitisation increased linearly with duration of hyperthermia for temperatures in the range 42.3-44.0 degrees C. Using temperatures below 42.0 degrees C, there was a saturation in effect for treatments longer than approximately 40-90 min, possibly due to the development of thermotolerance. The thermoradiosensitisation isoeffect curve relating heating time with temperature was biphasic with the transition occurring between 41.8 and 42.0 degrees C. For temperatures above the transition, a 1 degree C change was equivalent to a factor of 2.6 in heating time; below the transition, a 1 degree C change was equivalent to a factor of 5.4. Time-temperature relationships for thermoradiosensitisation in other rodent tissues are reviewed and compared with the general relationships for direct thermal injury, previously derived from experimental studies. The results are discussed with relevance to the interpretation of in vivo thermal enhancement of radiation injury.