Effect of 42°C Hyperthermia on Murine Normal and Tumor Tissues¹

The effect of one or two heat treatments at 42.0°C was studied in murine normal and tumor tissues. Early-generation isotransplants of a spontaneous fibrosarcoma, FSa-II tumors, were used. Single-cell suspension was transplanted into the mouse foot. Tumor growth time, the time required for half the treated tumors to reach 1000 cu mm from treatment day was the end point. For normal tissue studies, the foot reaction was scored according to our numerical score system. Hyperthermia was given in a constant temperature water bath. Tumors were treated when they reached an average diameter of 4 (35 cu mm) or 8 mm (270 cu mm). The 4-mm tumor responded poorly to a single heat treatment at 42.0°C, while the 8-mm tumor showed a substantial initial response, followed by the development of thermal resistance. The dose-response curve for the foot reaction was characterized by a large shoulder followed by a linear relationship. Thermal resistance developed in the 8-mm tumor following a continuous treatment of 150 min while in the foot tissue, 800 min were required before the development of thermal resistance.

The kinetics of thermal resistance were studied following the first dose of 150 min. Substantial resistance developed in both 4- and 8-mm tumors, as well as in the foot tissue, and reached maximum within 1 day. The decay of thermal resistance in the 8-mm tumor and in the foot was incomplete even at 5 days after the first heat dose, while the analysis was difficult for the 4-mm tumor because of continuous tumor growth. Comparison with treatments at 43.5°C and 45.5°C gave a conclusion that (a) a short single heat treatment of the 8-mm tumor at 42.0°C (below 43.0°C) resulted in a differential response between tumor and foot tissues, but a longer treatment did not; (b) the treatment temperature above 43.0°C was highly recommended; and (c) fractionated heat treatment at 42.0°C was not the choice of treatment for both 4- and 8-mm tumors.