Changes in thermosensitivity of mouse mammary carcinoma following hyperthermia in vivo.

The time course of change in thermosensitivity of SCK tumor cells in vivo was investigated following preheating at 43.5 degrees for 30 min. At varying times after the preheating with water bath, tumors were subjected to graded doses of second heating at 43.5 degrees in vivo, and cell survival was determined by using in vitro cloning method. Thermosensitivity of the tumor cells in vivo [duration of heating for exponential inactivation of cells to 1/e (Do): 15.5 min] gradually increased after the preheating, reaching a maximum increase at 5 hr (Do: 7.5 min), and then decreased thereafter, due probably to a development of thermotolerance. Maximum thermotolerance was observed at 12 hr after the preheating, leading to a 3-fold increase in Do (48 min). The thermotolerance gradually decayed for several days thereafter. The initial increase in thermosensitivity might be attributed to the acidic and nutritionally deprived intratumor environment as a result of vascular damage in heated tumor. It appears that thermotolerance gradually develops as time elapses and that it eventually overcomes the thermal sensitization of tumor cells in vivo.