The effect of step-down heating on murine normal and tumor tissues

Cultured cells can be sensitized to low-temperature hyperthermia (below 43.0 degrees C) by a prior heat shock at a high temperature (above 43.0 degrees C) if the heat above 43.0 degrees C is immediately followed by the heat below 43.0 degrees C. This effect has been termed step-down heating (SDH). We have studied the effect of SDH on the response of murine tumor and normal tissues treated at 45.5 degrees C. Animal tumors were eighth-generation isotransplants of a spontaneous fibrosarcoma in C3Hf/Sed. mice. Tumor response was studied by TG (tumor growth) time assay, i.e., determination of the time required for half the treated tumors to reach 1000 mm3 from the first day of treatment. Normal tissue response was studied in the mouse foot. End point was the time to induction of a score 4.0 (loss of a toe) or greater reaction in half the treated animals, RD50. The SDH at 41.0 degrees C sensitized the response of tumor and normal tissues to 45.5 degrees C. The enhancement ratios were congruent to 1.7 for both tissues, indicating no differential sensitization between tumor and normal tissues. No sensitization was observed if the SDH was given immediately after a second dose of 45.5 degrees C given 6 hr to 5 days following the first dose of 10 min at 45.5 degrees C. The SDH appeared not to inhibit the development of thermal resistance as evidenced by no appreciable changes in the thermal resistance ratio.