Importance of preheating temperature and time for the induction of thermotolerance in a solid tumour in vivo.

The importance of the priming heat treatment temperature and heating time for the degree and kinetics of thermotolerance was investigated in a C3H mammary carcinoma inoculated into the feet of CDF1 mice. A single heat treatment in the range 41.5-44.5 degrees C resulted in a linear relationship between heating time and tumour growth time (i.e. the time for tumours to reach a volume five times that of the first treatment day). An Arrhenius plot showed an inflection point at 42.5 degrees C with activation energies of 635 and 1508 kJ/mol, respectively, above and below 42.5 degrees C. The degree and kinetics of thermotolerance were independent of the preheating temperature, if the heating time was adjusted to give the same level of heat damage. A pretreatment at these temperatures with a tumour growth time of approximately 10 days, equivalent to 30 min at 43.5 degrees C, resulted in maximal thermotolerance at a 16-h interval with a thermotolerance ratio (TTRmax) of approximately 5.2. Preheating of the tumours at 43.5 degrees C for 3.5, 7.5, 15, 30, or 45 min, showed that if the preheating time was increased, both the TTRmax and the time interval necessary to develop TTRmax increased, both being linear functions of the duration of the preheating time. Maximal thermotolerance was obtained at intervals of 2, 4, 8, 16, and 28 h with TTRmax of 1.6, 2.2, 3.7, 5.2, and 7.7, respectively.