Effects of step-down and step-up heating on the development of thermotolerance in a C3H mammary carcinoma in vivo.

The effects of step-down (SDH) and step-up heating (SUH) on the development of thermotolerance were investigated in a C3H mammary carcinoma in vivo. The endpoint was tumour growth time, i.e. the time for a tumour to reach a volume five times that of the first treatment day. SDH consisted of 44.5 degrees C/5 min followed immediately by 41.0 degrees C/120 min. SUH consisted of the same heat treatments but in reverse sequence. Thermotolerance was detected by subsequent heating at 43.5 degrees C at variable intervals following the primary SDH or SUH. The degree of thermotolerance was quantified by the thermotolerance ratio (TTR) calculated as a ratio between the slope of the dose-response curve for tumours heated at 43.5 degrees C and tumours preheated with either SDH or SUH followed by 43.5 degrees C. Both SDH and SUH induced thermotolerance. However, the maximal degree of thermotolerance and the time interval to reach maximum thermotolerance were different. For SUH maximal thermotolerance was observed at 8 h with a TTR of 3.6. For SUH, thermotolerance peaked at 24-28 h with a TTR of 7.3. In both cases thermotolerance had decayed with a 120 h interval. The SDH priming induced about 2.5 times more heat damage than SUH. The results are therefore in agreement with previous data obtained in the same tumour model by single heating showing that both the degree and the time to reach maximal thermotolerance increases with pretreatment heat damage. In addition, the results indicate that thermotolerance and thermosensitization are independent phenomena.