G1 AND G2 CHECKPOINTS IN IRRADIATED CELLS

University Of California Irvine, Irvine CA

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Abstract

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.