Analysis of survival curves related to the spatial distribution and reparability of DNA damage

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  • DNA損傷の空間分布と難修復性を考慮した生存率曲線の解析

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Abstract

In general, survival curves of mammalian cells can be fit by linear-quadratic model. The quadratic term has been related to the lethal damage as a result of interaction of two damages in previous biophysical models. Unrepairable double-strand breaks (DSB) have been considered to be most responsible for cell lethality. However, it is still open question that what is the lethal damage and what kind of condition can be related to the linear and quadratic terms of the lethal damage. We have been obtained detail information on initial DNA damage by track structure simulation method. According to the simulation result, the increase of the complexity of initial DNA damage and cell lethality shows partially similar trend in their LET dependence. The purpose of this study is to elucidate and modeling the relationship between initial DNA damage and cell lethality. Here, the yield of lethal damage is estimated from experimentally obtained survival curves using linear-quadratic model. The estimated yields are compared with the simulated DNA spectrum and the spatial distribution such as the distance between damages in cell nucleus. From the comparison, the condition of initial damage related to the cell lethality is examined. In particular, LET and cell cycle dependent of survival curves are focused relating to the initial DNA damage pattern and repair pathways, respectively.

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