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

Watanabe, Ritsuko; Yokoya, Akinari; Suzuki, Masao*; Tsuruoka, Chizuru*; Hirayama, Ryoichi*; Furusawa, Yoshiya*

In general, survival curves of mammalian cells can be fit by linear-quadratic model. 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. 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 discussed relating to the initial DNA damage pattern and repair pathways, respectively.