Long-term observation of mouse foot reaction after hyperthermia: hyperthermia may or may not be carcinogenic?

A renewed interest in hyperthermia as a potential method of cancer therapy has stimulated biological studies on the thermal effect. We have studied the response of animal tumours and normal tissues to elevated temperature. In a series of experiments, animals which had received hyperthermia to their feet were observed until their spontaneous death in order to investigate possible hyperthermic late effects including carcinogenesis. The animals were C3Hf/Sed mice derived from our defined flora colony. They were kept in our animal facility where the defined flora conditions were maintained. The tumour was a 4th generation isotransplant of a methylcholanthrene- induced fibrosarcoma (FSa-I) which was moderately immunogenic (Suit et al., 1976). Tumours were treated at an average diameter of 6 mm. Hyperthermia was given by immersing the feet in a water bath where 43.5 ± 0.1°C was maintained by a Haake Model E-52 constant temperature circulator (West Germany). Each mouse was held in an individual holder without anaesthesia. The right foot was kept in position by taping the hind leg to a flat holder arm which was wider than the animal's leg. This procedure did not cause occlusion of the blood vessels. A total of 113 mice were used. Among them, 58 received single treatment to their normal feet and 55 received treatment to tumour-bearing feet. Animals which developed recurrences(12 mice) or metastases (two mice) were excluded from this study. Therefore, a total of 99 mice were observed until death.