| The use of hyperthermia in combination with radiation therapy may be improved with a thorough understanding of the cellular mechanism of thermal radiosensitization. It is thought that the mechanism of thermal radiosensitization is related to the inhibition of repair of radiation-induced DNA damage by heat. Due to the apparent role of the gene p21/WAF1/CIP1 in the repair of radiation-induced DNA damage, its involvement in thermal radiosensitzation was, therefore, investigated in this thesis. Two human colorectal cancer cell lines were used, both of which have wt p53 status but one was p21/WAF1/CIP1 deficient and the other was p21/WAF1/CIP1 proficient. I found no significant difference in the response of the two cell lines to exposure to 250 kV x-rays nor to hyperthermia treatments of two hours at 42°C or thirty minutes at 44°C. In addition, there was no difference in the clonogenic survival of both cell lines to hyperthermia before or after irradiation for both hyperthermia temperatures. Comparison of thermal enhancement ratios (TERs) showed that there was no difference in the amount of thermal radiosensitization induced in either cell line. The induction and subsequent repair of DNA double strand breaks, as measured by clamped homogenous gel electrophoresis (CHEF) was the same in both cell lines. This finding strongly suggests that the gene p21/WAF1/CIP1 does not have an effect on the degree of thermal radiosensitization expressed in these two cell lines. |
