Thermotolerance in preirradiated intestine and its influence on time-temperature relationships.

The crypt compartment of mouse jejunum showed a transient increase in thermal susceptibility approximately 10 days after moderate X-ray doses to the abdomen (9-10 Gy). The increase in response was manifest as an increase in slope of the crypt dose-response curve but was limited to temperatures below 43 degrees C. As a result, the 43 degrees C inflexion in the Arrhenius plot (the relationship between treatment time and temperature) for thermal sensitivity of crypts was eliminated in preirradiated tissue, and the curve became monophasic over the range 42.0-44.5 degrees C. At temperatures below 42 degrees C, the curve again deviated. At supranormal temperatures of 42 degrees C and below, the durations of hyperthermia needed for measurable effect were sufficient to allow thermotolerance to be expressed within the heating period. Neither the threshold heating times nor this thermotolerance were affected by prior irradiation. In the temperature range 42-43 degrees C, an earlier development of thermotolerance could be demonstrated in control tissue by challenging with an acute high-temperature heat treatment. This thermotolerance was eliminated in preirradiated tissue, resulting in the apparent increase in sensitivity. The findings support the view that the complex nature of the time-temperature relationship seen in normal tissue in vivo is a manifestation of the ability of the tissue to progressively acquire a thermotolerant state during treatment at temperatures below approximately 43 degrees C, so that the "intrinsic" sensitivity is modulated while being assessed.