Gerweck L E, Jennings M, Richards B
Cancer Res. 1980 Nov;40(11):4019-24.
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.
测定了暴露于42摄氏度的中国仓鼠卵巢细胞耐热性的发展和丧失的时间进程。研究了pH对正常细胞和耐热细胞热敏感性的影响。在pH 7.4条件下，细胞接受单次分级热处理，处理3至4小时后存活率降至5%至10%。继续加热4至5小时，存活率仅再降低1至2倍。在pH 6.7条件下，细胞接受单次热处理，处理3小时后存活率显著降低至约0.02%，直到存活率降至约0.001%才出现对进一步杀伤的抗性。细胞最初在pH 7.4条件下加热3小时，然后在37摄氏度下储存，在长达48小时后仍对额外处理具有抗性。耐热性在初始处理72小时后开始衰退，当两次处理间隔144小时时耐热性丧失。无论第二次处理时的pH如何，均观察到对第二次处理的显著抗性。平行研究还证实，加热细胞的存活后代在热刺激后不止一代仍对高温具有抗性。这些研究表明，当分次治疗间隔足够长以至于耐热性在两次治疗之间衰退时，肿瘤中出现的低pH条件可能会对反应产生最大影响。
