Influence of pH on the response of cells to single and split doses of hyperthermia

The time course of development and loss of thermotolerance in Chinese hamster ovary cells exposed to 42 degrees was determined. The influence of pH on the heat sensitivity of normal and thermotolerant cells was examined. Exposure of cells to single graded heat treatments at pH 7.4 resulted in a decrease in survival to 5 to 10% after 3 to 4 hr treatment. Continued heating for an additional 4 to 5 hr resulted in an additional decrease in survival by a factor of only 1 to 2. At pH 6.7, exposure of cells to single heat treatments caused a marked reduction in survival to congruent to 0.02% after 3 hr treatment, and resistance to further killing was not evident until survival decreased to congruent to 0.001%. Cells initially heated at pH 7.4 for 3 hr and then stored at 37 degrees remained resistant to additional treatment for up to 48 hr later. Thermotolerance began to decay 72 hr after the initial treatment and was lost when 144 hr separated the treatments. The marked resistance to second treatments was observed irrespective of the pH at the time of the second treatment. Parallel studies also established that the viable progeny of heated cells remained resistant to hyperthermia for more than one postheat generation. These studies suggest that low pH conditions occurring in tumors may be expected to maximally influence response when fractionation intervals are sufficiently long that thermotolerance decays between treatments.