Difference in the thermotolerance of mouse mammary carcinoma cells in vivo and in vitro.

The kinetics of thermotolerance development were compared for cells in the SCK mammary carcinoma of A/J mice, and the same cells cultured in vitro. Tumors in the legs of mice or cells in culture flasks were conditioned with heat in a water bath at 43 degrees C for 30 min and the cells were left in the tumors or the culture flasks for various lengths of time after heat conditioning. The magnitude of thermotolerance was determined by preparing single cells and subjecting them to a test heating in a controlled environment in vitro at 43 degrees C, and the survival of the cells was determined by measuring the colony-forming ability in vitro. Thermotolerance in tumors reached its maximum 12 h after heat conditioning, at which time the survival response was characterized by Do (the duration of heating required for exponential cell inactivation to 1/e) of 116 min. This changed to a Do of 170 min when the cells in tumors were incubated in culture medium of neutral pH during the development of thermotolerance. In contrast, the thermotolerance of cells cultured in vitro was fully developed within 8 h, at which time the Do was 306 min. The kinetics of thermotolerance development, therefore, varied significantly between the cells of the same origin but grown in vivo or in vitro. Killing of tumor cells in vivo caused by the heat-conditioning dose was about three times greater than that for tumor cells in vitro, but the greater damage did not result in a greater development of thermotolerance. The above results indicate that the development of thermotolerance in tumors is suppressed by the influence of intratumor environment.