RADIOSENSITIZATION AND CHEMOSENSITIZATION OF AERATED AND HYPOXIC MAMMALIAN CELLS

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The major objectives of this project are to identify approaches that will result in radiation enhancement of cell killing both in aerobic and hypoxic conditions and to better understand mechanisms of radiosensitization. Much of our previous work identified intracellular glutathione (GSH) as important in governing the cytotoxicity of certain chemotherapy drugs and hypoxic cell radiation sensitizers. We have recently shown that the chemotherapy drug paclitaxel (Taxoltm) is a radiation sensitizer for a number of different human cancer cell lines. Interestingly, paclitaxel radiosensitization was both concentration and time dependent and was observed in some but not all human tumor cell lines evaluated. Paclitaxel treatment leads to a pronounced G2/Mblock in the cell cycle. Cells in G2/M block are more sensitive to radiation than are cells in other phases of the cell cycle. Thus, our findings that paclitaxel sensitizes some but not all human cancer cell lines, despite the fact that all cell lines are blocked in G2/M, has interesting implications toward better defining the radiosensitization in radiosensitive phases of the cell cycle. Future studies will be directed toward evaluating paclitaxel as a radiosensitizer in an in vivo xenograft tumor model.