RADIOSENSITIZATION AND CHEMOSENSITIZATION OF AERATED AND HYPOXIC MAMMALIAN CELLS

该项目的主要目标是确定将 导致在有氧和无氧状态下细胞杀伤的辐射增强 为了更好地了解低氧条件下的缺氧机制 放射增敏。我们之前的许多工作都确定了细胞内 谷胱甘肽(GSH)在调节某些特定细胞毒性中的重要作用 化疗药物和低氧细胞辐射增敏剂。我们有 最近有研究表明，化疗药物紫杉醇(Taxoltm)是一种 多种不同人类癌细胞系的辐射增敏剂。 有趣的是，紫杉醇的放射增敏作用 并在部分但不是全部人类肿瘤细胞中观察到 已评估行。紫杉醇治疗导致明显的G2/M期阻滞 在细胞周期中。处于G2/M期的细胞对辐射更敏感 而不是处于细胞周期其他阶段的细胞。因此，我们的发现 紫杉醇使一些但不是所有的人类癌细胞株变得敏感， 尽管所有细胞株都被阻断在G2/M期，但这一点很有趣 对更好地定义放射增敏的影响 细胞周期的辐射敏感期。未来的研究将定向 评价紫杉醇在体内异种移植瘤中的放射增敏作用 肿瘤模型。

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.