Correlation between thermal radiosensitization and heat-induced loss of DNA polymerase beta activity in CHO cells

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 beta activity. Thermal radiosensitization was quantified by the thermal enhancement ratio TER10% determined on the 10% survival level and by the parameters alpha and beta obtained from fitting cellular survival data to the equation -ln(S/S0) = alpha D + beta D2. The values for TER10% and the alpha-term showed only a poor correlation with the inverse of polymerase beta activity; the data for single heating at temperatures exceeding 41.5 degrees C and the data for thermotolerant cells fell on the same straight line, whereas for single heating at T < or = 41.5 degrees C and for cells exposed to a high-to-low temperature sequence (step-down heating) the increase in TER10% and alpha was much steeper than found for the other heat treatments. By contrast, a linear relationship was shown to exist between the beta-term of cellular radiosensitivity and the loss of polymerase beta 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 beta-term observed after combined treatment with heat and radiation might be causally related to the heat-induced loss of polymerase beta activity.