Step-down heating of CHO cells at 37.5-39 degrees C

The thermosensitizing effect of step-down heating was studied using Chinese hamster ovary (CHO) cells. Exponentially growing cells were given priming heat treatments at 43 degrees C for 45 or 90 min, immediately followed by a second exposure to a temperature ranging from 37.5 to 39 degrees C. The measured rates of cell killing, 1/D0, increased exponentially with temperature; the slopes correspond to Arrhenius activation energies of Ea = 1200 +/- 150 kJ mol-1 and Ea = 1275 +/- 125 kJ mol-1 for cells preheated at 43 degrees C for 45 or 90 min, respectively. For the temperature range 39-43 degrees C an activation energy of Ea = 561 +/- 24 kJ mol-1 was obtained for step-down heated cells (43 degrees C, 45 min followed by T = 39-43 degrees C). These results indicate that there is a 'second inflection point' at 39 degrees C on the Arrhenius curve for step-down heating of CHO cells. Data evaluation using a mathematical model published previously (H. Jung, Radiation Research, 106, 56-72, 1986) showed that the rate constant c for the conversion of nonlethal lesions into lethal events increased with an activation energy of Ea = 1520 +/- 140 kJ mol-1 in the temperature range from 37.5-39 degrees C. For 39-45 degrees C the activation energy for c was Ea = 360 +/- 26 kJ mol-1, indicating that the temperature dependence of c shows a break at 39 degrees C similar to that observed on the 1/D0 Arrhenius plot.