The objective of this research is to determine the relative importance of various cellular processes in affecting tumor response to both sparsely and highly ionizing radiation. This is accomplished by using a well-characterized animal tumor system (the R-1 sarcoma in the WAG/Rij rat). The response from heavy charged particle radiation available at the Berkeley Bevalac is compared with the response from 225-kVp X rays. The studies are designed to provide information on the time course of the following cellular processes in irradiated tumors: repopulation, repair of potentially lethal damage, cell phase-specific survival and rates of reoxygenation. Repopulation is studied by measuring the fraction of clonogenic cells versus time by means of the tumor excision assay. Repair of potentially lethal damage is measured by the addition of the drug Beta-ara-A at a series of times postirradiation. Cell phase-specific survival is measured by introducing the Hoescht stain 33342 after tumor excision and sorting the cell population into G1, S and G2+M fractions with a FACS flow cytometer. Reoxygenation is measured via the excision assay method. The data gathered will be used to further develop a cell-kinetic model of tumor volume response after irradiation with high- and low-LET radiation. This project will provide an increased understanding of the relative importance of these processes in tumor response. This information will be useful to the heavy-charged particle radiotherapy program presently being conducted at the Bevalac heavy-ion accelerator.
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