Effect of chronic thermotolerance on thermosensitization in Chinese hamster ovary cells studied at various temperatures

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Abstract
The effect of chronic thermotolerance on the thermal responses of Chinese hamster ovary (CHO) cells to single and step-down heating was studied. Thermotolerance was induced by pre-heating exponentially growing cells at 39°C for 9 h, followed by test treatments for variable times at temperatures ranging from 39 to 43 °C. In the temperature range studied, the heat sensitivity of thermotolerant CHO cells was characterized by an Arrhenius activation energy of Ea=1175 ± 40 kJ/mol. This value agreed well with Ea = 1180 ± 45 kJ/mol measured after single heating, indicating that the induction of chronic thermotolerance did not affect the activation energy for cell killing by heat. Thermosensitization was studied after a priming treatment at 43°C for 50 min followed by step-down heating at temperatures ranging from 39 to 43°C. The temperature dependence of the thermal response after step-down heating was characterized by an activation energy of Ea =490 ± 17 kJ/mol. When the cells were pre-treated for 1–16 h at 39°C prior to step-down heating (43°C, 50 min, followed by graded exposure to 39–43°C), the activation energy was gradually enhanced and approached Ea = 825 ± 42 kJ/mol for 39 z°C, 16 h. This change in Ea reflects the effect of thermotolerance on the priming treatment at 43°C for 50 min, whereas the effect on the final test treatment resulted in a parallel shift of the Arrhenius curve without changing the slope, indicating that the effect of thermotolerance on the priming and the test treatment is expressed in the Arrhenius diagram in different ways.