Response of cells to hyperthermia under acute and chronic hypoxic conditions.
The lethal response of Chinese hamster cells heated to 42 degrees was determined following 0 to 30 hr culturing under hypoxic conditions. Oxygenated and acutely hypoxic cells were equally sensitive to hyperthermia; however, sensitivity increased with the time of culturing under hypoxic conditions prior to treatment. Three hr at 42 degrees resulted in a surviving fraction of approximately or equal to 0.1 under acute hypoxic conditions and less than 0.001 for cells cultured for 30 hr under oxygen-deprived conditions before the heat treatment. The increased sensitivity to hyperthermia was 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. However, even under fully controlled pH conditions, prolonged oxygen deprivation increased hyperthermic cell killing by a factor of approximately or equal to 5. This effect was not reversed by returning the cells to normal oxygen tension prior to treatment. These data demonstrate that tumorlike microenvironmental conditions (reduced O2 tension and pH) substantially increase the sensitivity of cells to 42 degrees hyperthermia.