G1 AND G2 CHECKPOINTS IN IRRADIATED CELLS

建议进行研究以深入了解分子遗传机制 辐射损伤处理的基础和辐射损伤的后果 这一过程。一对同基因人类的初步研究 仅在P53状态不同的纤维肉瘤细胞株 在以下观察中：1)G1和G2检查点似乎 具有一定的冗余性，2)G2检查点似乎两者都有 P53依赖和非依赖成分；3)原癌基因 Stathmin似乎改变了P53介导的细胞周期停滞。实验 建议使用同步细胞群来研究其作用 染色体畸变诱导、克隆形成中的G1和G2检查点 存活、突变诱导与细胞周期动力学 进展，都是在电离辐射之后。这些实验 应提供有关细胞周期检查点对 辐射诱导的细胞致死和遗传不稳定性。 对G1期延长逮捕的机制进行了调查 正常人二倍体皮肤成纤维细胞有可能进一步 阐明各步骤在整合素信号转导中的作用 影响辐射诱导的细胞周期停滞和遗传的途径 稳定性。

Studies are proposed to gain insight into molecular genetic mechanisms underlying the processing of radiation damage and the consequences of that processing. Preliminary studies with a pair of isogeneic human fibrosarcoma cell lines differing only in their p53 status have resulted in the following observations: 1) The G1 and G2 checkpoints appear to have a certain redundancy, 2) The G2 checkpoint appears to have both p53-dependent and - independent components, and 3) The proto-oncogene stathmin appears to alter p53-mediated cell cycle arrest. Experiments are proposed using synchronized cell populations to investigate the role of G1 and G2 checkpoints in chromosome aberration induction, clonogenic survival, mutation induction, and the kinetics of cell cycle progression, all following ionizing irradiation. These experiments should provide information on the impact of cell cycle checkpoints on radiation-induced cellular lethality and genetic instability. Investigations into the mechanism underlying the prolonged G1 arrest in normal human diploid skin fibroblasts have the potential to further elucidate the role of various steps in the integrin signal transduction pathway in influencing radiation-induced cell cycle arrest and genetic stability.