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A Framework for Analysis of Abortive Colony Size Distributions Using a Model of Branching Processes in Irradiated Normal Human Fibroblasts

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  • Tetsuya Sakashita
  • Nobuyuki Hamada
  • Isao Kawaguchi
  • Noriyuki B Ouchi
  • Takamitsu Hara
  • Yasuhiko Kobayashi
  • Kimiaki Saito

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. Methodology/Principal Findings: 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 (

Suggested Citation

  • Tetsuya Sakashita & Nobuyuki Hamada & Isao Kawaguchi & Noriyuki B Ouchi & Takamitsu Hara & Yasuhiko Kobayashi & Kimiaki Saito, 2013. "A Framework for Analysis of Abortive Colony Size Distributions Using a Model of Branching Processes in Irradiated Normal Human Fibroblasts," PLOS ONE, Public Library of Science, vol. 8(7), pages 1-10, July.
    • Handle: RePEc:plo:pone00:0070291
    DOI: 10.1371/journal.pone.0070291
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    Cited by:

    1. Yuki Fujimichi & Nobuyuki Hamada, 2014. "Ionizing Irradiation Not Only Inactivates Clonogenic Potential in Primary Normal Human Diploid Lens Epithelial Cells but Also Stimulates Cell Proliferation in a Subset of This Population," PLOS ONE, Public Library of Science, vol. 9(5), pages 1-10, May.

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