LOW DOSE IRRADIATION AND HYPERTHERMIA IN HUMAN TUMOURS

近距离放射治疗（插入放射性同位素进行腔间或腔间照射）

Brachytherapy (irradiation by inserted radioisotopes interacavitary or interstitial) is now being extensively used in the treatment of cancer because of improved dose distribution and increased normal tissue sparing. At the effective dose rates achieved in conventional brachytherapy (0.1 - 3.09 Cgy/min) extensive tissue sparing occurs in both normal and tumor tissues due to recovery from sublethal radiation damage (SLD). our in vitro results have shown that hyperthermia can inhibit such recovery. The goal of this project is to evaluate the potential for localized hyperthermia (41-45C) to improve the outcome of brachytherapy in cancer treatment. Specific Aims: 1) Evaluate the hyperthermia and low dose rate radiation responses of five human cell lines (1 normal and 4 tumor derived) which have different capacities for recovery of sublethal radiation damage. 2) Determine the degree of thermal radiosensitization at low radiation dose rates and relate this to SLD repair capacity and its inhibition in the 5 human cell lines. 3) Determine the modifying effects of cell conditions such as contact and Ph on the responses to hyperthermia and radiation. 4) Assess the activity of DNA polymerases as indicators of thermal radiosensitization with the objective that these indicators may be used clinically to determine potential thermal enhancement of brachytherapy. Presently no data has been reported on thermal enhancement of low dose rate irradiation in human tumor cells. Clinical trials show varying degrees of efficacy and our experiments evaluating time temperature and sequencing relationships and effect on polymerase activity vs. radiation sensitization will provide guidance to optimization of combination therapy and potential for predicting clinical efficacy. Techniques to be used: cell survival, low dose rate irradiation, hyperthermia, flow cytometry, polymerase analysis, Ph modulation.