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Heat Sensitivity and Thermotolerance in Cells from Five Human Melanoma Xenografts¹

Norsk Hydro's Institute for Cancer Research and the Norwegian Cancer Society, the Norwegian Radium Hospital, Montebello, Oslo 3, Norway

The heat sensitivity and the development of thermotolerance in cells from five human melanoma xenografts were studied. The cells were heated in vitro in a water bath, and the colony-forming ability of the cells was assayed in soft agar. The D₀ values of the heat survival curves were in the ranges of 44 to 123 min (42.5°), 22.3 to 63.3 min (43.5°), and 6.0 to 22.1 min (44.5°). The order of the heat sensitivity of the five melanomas was not the same at the three temperatures studied. Cells from all melanomas developed thermotolerance during protracted treatments at 42.5°. Thermotolerance was also studied by exposing cells to a priming heat treatment of 43.5° for 60 min and, after different fractionation intervals at 37°, to graded heat treatments at 43.5°. The ratio of the slopes of the survival curves for preheated and single-heated cells, i.e., the thermotolerance ratio (TTR), was used as a quantitative measure of the thermotolerance. For all melanomas, the TTR reached a maximum at 24 hr and then decayed slowly. The maximum TTR values ranged from about 2.9 to about 10.2. There was no correlation between the maximum TTR and the heat sensitivity for the five melanomas. Thus, the magnitude and the kinetics of thermotolerance in tumors can probably not be predicted from the surviving fraction after the priming treatment. The heat sensitivity of the tumor cells and their ability to develop thermotolerance are probably among the factors which are decisive for the response of tumors to fractionated heat treatments. The large variability in these parameters observed in the present work indicates that the response to heat may vary considerably among tumors of the same histological type in different patients.

¹ Financial support was received from the Norwegian Cancer Society, the Norwegian Research Council for Science and the Humanities, and the Nansen Scientific Fund.

² To whom requests for reprints should be addressed.

Received 3/23/84. Accepted 6/22/84.