The heat response of the SCK mammary carcinoma of A/J mice was studied in vivo and in vitro. Solid tumors or tumor cells in culture were heated in a water bath and cell survival was determined by clonogenicity in vitro. Cells in tumors were much more sensitive to heat than cells in culture. To eliminate vascular effects, tumors were dissociated into small fragments and the tumor fragments were heated in vitro, so that cells were heated while in contact with neighbors and in a complete medium. Cells in tumor fragments were as sensitive to heat as cells in tumors, even though vascular effects during heat exposure were excluded. The heat-sensitive tumor fragments gradually became heat resistant during 3 h of incubation in a complete medium at physiological temperature. The transition from a heat-sensitive to a heat-resistant state was not correlated with the development of thermotolerance or stress-related proteins. The transition was inhibited when the extracellular environment was made acidic or hypoxic but not when it was glucose and serum deprived. These results suggest that SCK tumor cells in vivo are sensitive to heat, and the heat-sensitive state appears to be established under the influence of the intratumor environment.

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