title: A framework for analysis of abortive colony size distributions using a model of branching processes in irradiated normal human fibroblasts.
abstract: BACKGROUND
  Clonogenicity gives important information about the cellular reproductive potential following ionizing irradiation, but an abortive colony that fails to continue to grow remains poorly characterized. It was recently reported that the fraction of abortive colonies increases with increasing dose. Thus, we set out to investigate the production kinetics of abortive colonies using a model of branching processes.
  
  
  RESULTS
  We firstly plotted the experimentally determined colony size distribution of abortive colonies in irradiated normal human fibroblasts, and found the linear relationship on the log-linear or 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, abortive colony size distribution (≤ 15 cells) and the surviving fraction were simulated by the Monte Carlo computational approach for colony expansion. Parameters estimated from the log-log fit demonstrated the good performance in both simulations than those from the log-linear fit. Radiation-induced RCD, i.e. excess probability, lasted over 16 generations and mainly consisted of two components in the early (<3 generations) and late phases. Intriguingly, the survival curve was sensitive to the excess probability over 5 generations, whereas abortive colony size distribution was robust against it. These results suggest that, whereas short-term RCD is critical to the abortive colony size distribution, long-lasting RCD is important for the dose response of the surviving fraction.
  
  
  CONCLUSIONS
  Our present model provides a single framework for understanding the behavior of primary cell colonies in culture following irradiation.
authors.affiliation: Microbeam Radiation Biology Group, Japan Atomic Energy Agency (JAEA), Gunma, Japan. sakashita.tetsuya@jaea.go.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sakashita
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamada
authors.forename: Isao
authors.initials: I
authors.lastname: Kawaguchi
authors.forename: Noriyuki B
authors.initials: NB
authors.lastname: Ouchi
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Hara
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Kimiaki
authors.initials: K
authors.lastname: Saito
mesh_terms: D016923:Cell Death / Q000528:radiation effects; D002460:Cell Line; D019070:Cell Lineage; D002470:Cell Survival / Q000528:radiation effects; D002999:Clone Cells; D003037:Cobalt Radioisotopes; D003198:Computer Simulation; D005347:Fibroblasts / Q000528:radiation effects*; D005720:Gamma Rays; D006801:Humans; D008954:Models, Biological; D008962:Models, Theoretical; D009010:Monte Carlo Method; D012044:Regression Analysis; D016019:Survival Analysis
chemical_list: D003037:Cobalt Radioisotopes
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