Radiotherapy is a central component of modern cancer treatment. Identification of patients most likely to benefit from treatment with ionizing radiation would greatly improve individual therapeutic success. We propose to investigate the hypothesis that the presence of radioresistant or repair-proficient cells in human tumors predicts radiotherapy failure. Therefore, we will establish early-passage cultures of human tumor cells derived from patients prior to radiotherapy and study the radiosensitivity and repair of radiation damage in these human tumor cells. Our studies will include: 1) determination of D-o, n- and the repair of sublethal x-ray damage in exponential cultures of these tumor cells; 2) determination of the repair of potentially lethal damage in plateau-phase cultures; 3) measurement of the induction and repair of DNA strand breaks employing DNA elution and chromosome aberration assays in both exponential and plateau-phase cultures; and 4) measurement of poly (ADP-ribose) activity and nicotinamide adenine dinucleotide (NAD+) content in the tumor cells before and after irradiation in exponential and plateau-phase cultures. These cellular, chromosomal and biochemical assays will be correlated with patient outcome, assessed in terms of local control as well as total patient survival time and disease-free interval following radiotherapy. It is expected that one or more of these biological assays will predict radiocurability in patients receiving radiotherapy.
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