Interaction of the effects of hyperthermia and ionizing radiation on cell survival

Chapter one contains a brief review of the literature concerning the effects of hyperthermia and radiation, on cellular reproductive integrity. Chapter two describes the cell line used and the physical and biological aspects of the experiments. The preliminary experiments of chapter three revealed that the experimental stability was adequate for inter-experiment comparisons, provided that sufficient control data were obtained. Further experiments provided a cursory examination of several aspects of the interaction between radiation, and hyperthermia. In chapter four, a simple sensitization model that would account for the observed results for any single value of the perturbing radiation or hyperthermia dose is developed. Using the concept of the survival surface, this simple model is expanded to simultaneously describe survivals for any combination of the radiation and hyperthermia dose. The resulting first order interaction model, while only approximately describing the survival surface, is nevertheless useful in providing a coherent picture of the results of chapter three. The interaction component of this model is first order in both hyperthermia exposure and radiation dose. The mechanism by which radiation contributes to the interaction was investigated by altering the radiation quality. The results of this investigation, presented in chapter five, suggest that high LET events contribute to the interaction. The mechanism by which hyperthermia contributes to the interaction was investigated by altering the hyperthermia temperature. A thermodynamic analysis of the data, presented in chapter six, reveals parallels with the effects of hyperthermia and radiation on protein, suggesting a possible involvment of protein denaturation in cell inactivation. Chapter seven contains concluding remarks and suggestions for extended applications of the survival surface approach. These include an in vivo application of the theory that might provide the data required for clinical application