Heat sensitivity and thermotolerance in vitro of human breast carcinoma, malignant melanoma and squamous cell carcinoma of the head and neck

Abstract

Heat sensitivity and the development of thermotolerance of cells isolated directly from surgical specimens of human breast carcinoma, malignant melanoma and squamous cell carcinoma of the head and neck were studied in vitro using the Courtenay soft agar colony assay. The plating efficiency of some of the tumours was sufficiently high (0.3-20.4%) for survival curves covering up to two to three decades to be established. Experiments repeated with cells stored in liquid nitrogen showed that the survival assay gave highly reproducible results. Heat sensitivity of thermotolerant cells was studied by giving cells a conditioning heat treatment of 43.5 degrees C for 60 min and, after incubation at 37 degrees C for 24 h, second graded heat treatments at 43.5 degrees C. Significant differences in heat sensitivity and development of thermotolerance between the three tumour types were not found. However, the heat sensitivity, whether the cells were thermotolerant or not, differed considerably among individual tumours of each histological category. Do at 43.5 degrees C was found to be in the ranges of 23-59 min (breast carcinoma), 20-63 min (malignant melanoma) and 20-57 min (squamous cell carcinoma) for single-heated cells and 105-476 min (breast carcinoma). 102-455 min (malignant melanoma) and 87-400 min (squamous cell carcinoma) for thermotolerant cells. The heat sensitivity of cells made thermotolerant showed no significant correlation to the surviving fraction after the conditioning heat treatment. The study indicated that histological category is a poor parameter for assessment of clinical heat responsiveness of tumours. Breast carcinoma, malignant melanoma and squamous cell carcinoma are probably, from a thermobiological point of view, equally good candidates for clinical trial aimed at studying the potential usefulness of hyperthermia as an adjunct to radiation therapy and/or chemotherapy. The large differences in heat sensitivity and development of thermotolerance observed among individual tumours, irrespective of histological origin, suggested that an in vitro predictive assay for heat responsiveness would be very useful for stratification purposes in such clinical trials.