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Computation Molecular Kinetics Model of HZE Induced Cell Cycle ArrestCell culture models play an important role in understanding the biological effectiveness of space radiation. High energy and charge (HZE) ions produce prolonged cell cycle arrests at the G1/S and G2/M transition points in the cell cycle. A detailed description of these phenomena is needed to integrate knowledge of the expression of DNA damage in surviving cells, including the determination of relative effectiveness factors between different types of radiation that produce differential types of DNA damage and arrest durations. We have developed a hierarchical kinetics model that tracks the distribution of cells in various cell phase compartments (early G1, late G1, S, G2, and M), however with transition rates that are controlled by rate-limiting steps in the kinetics of cyclin-cdk's interactions with their families of transcription factors and inhibitor molecules. The coupling of damaged DNA molecules to the downstream cyclin-cdk inhibitors is achieved through a description of the DNA-PK and ATM signaling pathways. For HZE irradiations we describe preliminary results, which introduce simulation of the stochastic nature of the number of direct particle traversals per cell in the modulation of cyclin-cdk and cell cycle population kinetics. Comparison of the model to data for fibroblast cells irradiated photons or HZE ions are described.
Document ID
20050220660
Acquisition Source
Johnson Space Center
Document Type
Conference Paper
Authors
Cucinotta, Francis A.
(NASA Johnson Space Center Houston, TX, United States)
Ren, Lei
(Universities Space Research Association Houston, TX, United States)
Date Acquired
August 23, 2013
Publication Date
January 1, 2004
Subject Category
Life Sciences (General)
Meeting Information
Meeting: 15th Annual NASA Space Radiation Health Investigator''s Workshop
Country: Unknown
Start Date: May 16, 2004
End Date: May 20, 2004
Sponsors: Department of Energy, Brookhaven National Lab., Universities Space Research Association, NASA Headquarters
Distribution Limits
Public
Copyright
Other

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