A Framework for understanding the production kinetics of abortive colony size distributions in irradiated normal human fibroblasts

Sakashita, Tetsuya; Hamada, Nobuyuki*; Kawaguchi, Isao*; Ouchi, Noriyuki; Hara, Takamitsu*; Kobayashi, Yasuhiko; Saito, Kimiaki  

The production kinetics of abortive colonies was investigated using a model of branching processes. We experimentally determined the colony size distribution of abortive colonies exposed to low linear energy transfer (LET) -rays, and found its linear relationship on the log-log plot. By applying the simple model of branching processes to the linear relationship, we found the persistent reproductive cell death (RCD) over several generations following irradiation. To verify the estimated probability of RCD, the Monte Carlo simulation was used. Radiation-induced RCD lasted over 16 generations and mainly consisted of two components in the early and late phases. Intriguingly, the survival curve was sensitive to the excess probability over 5 generations. Such framework for the combined analysis with a branching process model and a colony formation assay was also applicable to determination of cellular responses to high-LET carbon-ion radiation.