R.D. Stewart, J.K. Shultis and B.A. Montelone, "A Cell Killing Model that Includes the Effects of Chromatin Structure. II. Proliferating Cells, accepted for presentation, 46th Annual Meeting of Radiation Research Society, 1998.

A molecular-level radiobiological model has been developed and used to investigate the biological basis for cell cycle effects in Chinese hamster V79 cells. The proposed model accounts for the heterogeneous formation and repair of DNA damage in heterochromatin, two types of euchromatin, and just-replicated nascent euchromatin. The proposed model also accounts for damage-induced cell cycle blocking, temporal changes in the structure of a cell's chromatin, and desynchronization effects in groups of proliferating cells.

Model sensitivity studies and comparisons of measured and calculated cell survival probabilities indicate the modeling at a molecular level of radiation-induced cell-killing effects in proliferating V79 cells has been successful. Model results suggest that cell cycle changes in chromatin structure produce cyclic changes in the initial yield of DNA damage per Gy per cell. These cyclic changes in the structure of the chromatin also produce cyclic changes in the rates of DNA damage repair and in the rate the initial DNA damage is converted into lethal types of DNA damage. It is concluded that these phenomena are responsible for observed cell cycle effects. Finally, calculations illustrating the model’s use to optimize dose-fractionation patterns in radiotherapy treatment protocols are presented and discussed.

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