Correlation between Thermal Radiosensitization and Heat-induced Loss of DNA Polymerase β Activity in CHO Cells

Abstract

The increase in radiosensitivity caused by various kinds of single and combined heat treatments was studied in CHO cells and related to the heat-induced loss of the DNA polymerase β activity. Thermal radiosensitization was quantified by the thermal enhancement ratio TER_10% determined on the 10% survival level and by the parameters α and β obtained from fitting cellular survival data to the equation − ln(S/S₀) = αD + βD². The values for TER_10% and the α-term showed only a poor correlation with the inverse of polymerase β activity; the data for single heating at temperatures exceeding 41·5°C and the data for thermotolerant cells fell on the same straight line, whereas for single heating at T ⩽ 41·5°C and for cells exposed to a high-to-low temperature sequence (step-down heating) the increase in TER_10% and α was much steeper than found for the other heat treatments. By contrast, a linear relationship was shown to exist between the β-term of cellular radiosensitivity and the loss of polymerase β activity as expressed by the reciprocal value of the enzyme activity. This relationship was the same for all kinds of heat treatments applied, suggesting that for CHO cells the increase in the β-term observed after combined treatment with heat and radiation might be causally related to the heat-induced loss of polymerase β activity.