The induction of thermotolerance in the ear of the mouse by fractionated hyperthermia

The development of thermotolerance in ears of mice was investigated after fractionated hyperthermia. Ears were heated at 43.5 degrees C by immersion in a water bath and the response was measured in terms of the heating time required to cause thermal necrosis in 50% of the ears (NT50). Three types of treatment were given: (1) single treatments, for which the NT50 was 42 minutes; (2) priming treatments, which caused little visible effect but induced thermotolerance. These treatments were given as 1-10 daily fractions, the total heating time ranging from 20-630 minutes; (3) test treatments which were given at various times after priming and were varied to estimate the NT50. Thermotolerance was defined as an increase in the test NT50 for preheated ears relative to the single treatment NT50. It has been suggested that thermotolerance induced by a single priming treatment may be increased by giving additional heat treatments which would not be tolerated by normal cells. In the mouse ear, the maximum thermotolerance induced by a single priming treatment of 20 min at 43.5 degrees C was seen after 24 hr when the test NT50 was about 2.5 times the single NT50. The effect of giving up to nine additional daily treatments of 70 min, each of which would cause necrosis in ears that had not received prior hyperthermia, was measured. The maximum thermotolerance observed was equal to that after a single 20 minute priming treatment but thermotolerance decreased as the number of 70 min treatments was increased from four to nine. The effects of repeating a treatment (20 min or 5 min) which was tolerated by normal ears and induced maximal or less than maximal resistance were compared. The interval between each fraction (24 hr or 12 hr respectively) was equal to the time at which maximal thermotolerance was observed after one treatment. For each regimen, the degree of resistance seen after 2 to 10 exposures was similar to that after the appropriate single treatment. This resistance was maintained throughout the course of priming treatment and decayed after the last fraction. Thus for this regimen, thermotolerance depended on the duration of each treatment rather than on the number of treatments given.