Radiotherapy is an important component of modern cancer treatment. Identification of patients most likely to benefit from treatment with ionizing radiation might improve the therapeutic ratio. We propose to continue to investigate the hypothesis that the presence of radioresistant and/or repair proficient cells in human tumors predicts radiotherapy failure. Therefore, we will establish early-passage cultures of human tumor cell lines from biopsies of head-and-neck carcinomas and soft-tissue sarcomas derived from patients prior to radiotherapy. We will then study the radiosensitivity and repair of radiation damage in these human tumor cells and correlate our in vitro findings with radiocurability measured in terms of local control and total survival. Our studies will include: 1) determination of D0, n, D derived from survival at doses of 100-1100 cGy (3 logs cell kill), survival at 200 cGy; 2) measurement of sublethal damage repair (SLDR) in exponentially-growing cultures of these early-passage tumor cells; determination of the repair of potentially lethal damage (PLDR) employing PLDR survival curves (100-1100 cGy) at 0 and 24 hrs. PLDR time and time course PLDR experiments following a single dose and subculture at various time points from plateau phase cultures; 3) measurement of the induction and rejoining of DNA double-strand breaks in first-passage, exponentially-growing cultures of human head-and-neck and soft-tissue sarcoma cell lines. The radiobiological parameter(s) that is(are) the biological basis of radiotherapy failure or success and predicts clinical outcome may emerge from our investigation.
Showing the most recent 10 out of 62 publications
