RESPONSE OF CELLS TO HYPERTHERMIA UNDER ACUTE AND CHRONIC HYPOXIC CONDITIONS

  • 1 January 1979
    • journal article
    • research article
    • Vol. 39  (3) , 966-972
Abstract
The lethal response of Chinese hamster [ovary CHO] cells heated to 42.degree. C was determined following 0-30 h culturing under hypoxic conditions. Oxygenated and acutely hypoxic cells were equally sensitive to hyperthermia; sensitivity increased with the time of culturing under hypoxic conditions prior to treatment. Three hours at 42.degree. C resulted in a surviving fraction of .simeq. 0.1 under acute hypoxic conditions and less than 0.001 for cells cultured for 30 h under O2-deprived conditions before the heat treatment. The increased sensitivity to hyperthermia was due in part to a decrease in the pH of the medium which occurred as a result of cell metabolism; this could be reversed by increasing pH to 7.3 immediately prior to heat treatment. Even under fully controlled pH conditions, prolonged O2 deprivation increased hyperthermic cell killing by a factor of .simeq. 5. This effect was not reversed by returning the cells to normal O2 tension prior to treatment. Tumorlike microenvironmental conditions (reduced O2 tension and pH) substantially increase the sensitivity of cells to 42.degree. C hyperthermia. [Applications to human cancer therapy were discussed.].

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