Effect of hyperthermia on the radiation response of the mouse jejunum

The experiments reported show that the effect of radiation on the gut mucosa may be significantly enhanced by moderate hyperthermia (41°-44°C) that is applied for 30 min before or after irradiation. The predominant effect of combined heat and radiation was to displace the radiation survival curves of jejunal crypt stem cells to the left without a significant change in slope. The degree of displacement was temperature-dependent from 41 to 44°C, and was greater when heating preceded irradiation. The thermal enhancement ratio (TER) for crypt stem cell survival is not constant but increases with higher surviving fractions. At the isoeffect level of 20 surviving stem cells per jejunal circumference, the TER reached a maximum of 4.7 when heating for 30 min at 44°C preceded irradiation. Although direct comparisons of published TER's for different tissues cannot be made because the levels of cellular survival to produce given endpoints differ, it appears that the gut may be particularly vulnerable to radiation damage when preheated to temperatures over 42°C. It is important for the safety of human combined modality studies first that specific information concerning the tolerance of all critical normal tissues to heat and irradiation be obtained, and second that the likelihood of an increase in TER with fractionated exposures to heat and irradiation be appreciated.