Similarity of Thermotolerance Characteristics in Heterogeneous Human Colon Tumor Subpopulations after Exposure to Fractionated Heat Doses (44°C)

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Abstract
We have studied the thermotolerance (TTR) responses of three tumor cell populations obtained from a heterogeneous human colon cancer after exposure to 44.degree. C water bath hyperthermia given in a split dose regimen. The cell populations studied consist of the original tumor line (DLD-1) obtained from surgical biopsy, and two subcloned populations termed clones A and D. All tumor lines were treated with initial heat doses at 44.degree. C which reduced the initial survival level to about 30, 10, or 1%, after which cultures were returned to 37.degree. C. Complete survival curves were then determined for all three lines as a function of time after the initial treatment (0, 2, 4, 8, 12, 14, 20, and 24 h), and the magnitude and kinetics of thermotolerance development and its decay were determined. It was found that the DLD-1 line was more heat sensitive and exhibited a lesser degree of induced thermotolerance than did the A and D subpopulations, indicating intraclonal heterogeneity. Also, the rate of thermotolerance induction, the maximal thermotolerance reached (TTRmax), and the rate of thermotolerance decay were strongly dependent upon the survival level produced by the initial heat exposure. The importance of these findings to the treatment of heterogeneous cancers by heat is discussed.