Thermotolerance kinetics and growth rate changes in the R1H tumour heated at 43°C

Abstract

R1H rhabdomyosarcomas implanted into the foot of the right hind leg of female WAG/Rij rats were exposed to fractionated hyperthermia at 43°C and the kinetics of thermotolerance and heat-induced growth rate changes were studied. Tumours of anaesthetized animals were exposed to heat by immersing the leg up to the thigh in a water bath. Tumour growth delay (TGD) and tumour volume doubling time were calculated from individual growth curves. After single heating, TGD increased with increasing heating time, the increase being linear for heating times exceeding 60min. Thermotolerance was induced by a priming heat treatment at 43°C for 60 min and the kinetics of development and decay was studied for fractionation intervals ranging from 4 to 144 h. After 4 h the thermal sensitivity of the tumours was enhanced by about 30 per cent, probably due to the sensitizing effect of heat-induced physiological alterations in the tumour tissue such as suboptimal environmental conditions caused by depressed blood flow. For longer time intervals thermotolerance developed and reached a maximum at 24 h where the thermotolerance ratio was 4·5 ± 1-5. From 24 to 144 h thermotolerance decayed exponentially with a half-time of 28 ± 8 h. Heat also affected the growth rate of the treated tumours. After single heat treatments at 43°C for 15·60 min the tumours grew faster than untreated control tumours. This change was statistically significant. After prolonged single heating, growth rate was found to be reduced. Tumour volume doubling time was not detectably changed after fractionated heat treatments.

Key Words:

• hyperthermia
• thermotolerance
• growth rate
• R1H tumour
• heat fractionation