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

Abstract

A molecular-level radiobiological model has been developed and used to investigate dose and dose-rate killing effects in stationary-phase Chinese hamster ovary (CHO) cells exposed to Cs-137 gamma rays. In this model, ionizing radiation initially produces double strand break (DSB) lesions which are later converted into lethal chromosome aberrations by two time-dependent processes: lesion fixation and pairwise DSB interaction. The lesion fixation process produces simple chromosome breaks, and the pairwise interaction process produces more complex exchange-type aberrations. The proposed model accounts for differences in the initial DSB yield (per Gy per bp) in three types of chromatin: heterochromatin, transcriptionally inactive chromatin, and transcriptionally active chromatin. The proposed model also allows a different DSB repair probability (rate) to be used for each of the three chromatin states.

With the same DNA lesion repair probability for all three chromatin states, no reasonable set of model parameters was found that could adequately explain the observed dose and dose-rate effects. However, calculated results obtained using a different repair probability for each chromatin state were in excellent agreement with measured data. Further analysis of dose and dose-rate effects with this model suggests that at least a portion of the DSBs responsible;e for the observed killing effects in stationary-phase CHO cells has a characteristic repair half-time greater than 7 hours.

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