Thermotolerance induced by fractionated hyperthermia: dependence of the interval between fractions

The induction of thermotolerance by fractionated hyperthermia was investigated in the mouse ear. Ears were heated at 43.5 degrees C by immersion in water. One to ten treatments of 20 min were followed by test treatments. Thermotolerance was assessed as the increase in the duration of the test treatment required for a thermal response in 50 per cent of the ears (NT50). A single treatment induced thermotolerance which reached a maximum at 24 h when the NT50 was increased by a factor of 2.4. The same maximum was observed after each fractionated treatment used in the present study. The time course of development, however, depended on the interval between fractions. (1) When the interval was too short to allow development of thermotolerance after a single fraction (4 h), thermotolerance was not induced during fractionated treatment but it developed during the first 24 h after treatment. (2) When the interval between fractions allowed the maximal development of thermotolerance (24 h), this maximum was maintained during fractionated treatment and persisted for 24 h after treatment. (3) When the interval allowed some decay of thermotolerance (72 or 168 h) there was a further increase to maximal thermotolerance after each fraction. The decay of thermotolerance from the maximum did not depend on the interval between fractions. These results indicate that the degree of thermotolerance may fluctuate during fractionated hyperthermia.