Step-down heating of CHO cells at 37.5–39° C

Abstract

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 °C for 45 or 90 min, immediately followed by a second exposure to a temperature ranging from 37–5 to 39°C. The measured rates of cell killing, 1/D₀, increased exponentially with temperature; the slopes correspond to Arrhenius activation energies of E_a=1200±150 kJ mol⁻¹ and E_a= 1275 ±125 kJ mol⁻¹ for cells preheated at 43°C for 45 or 90 min, respectively. For the temperature range 39–43°C an activation energy of E_a=561 ±24 kJ mol⁻¹ was obtained for step-down heated cells (43°C, 45 min followed by T=39–43°C). These results indicate that there is a ‘second inflection point’ at 39°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 E_a= 1520±140 kJ mol⁻¹ in the temperature range from 37.5–39°C. For 39–45°C the activation energy for c was E_a=360±26 kJ mol⁻¹, indicating that the temperature dependence of c shows a break at 39°C similar to that observed on the 1/D₀ Arrhenius plot.

Key Words:

• hyperthermia
• step-down heating
• thermosensitization
• Arrhenius activation energy.