title: A branching process model for the analysis of abortive colony size distributions in carbon ion-irradiated normal human fibroblasts.
abstract: A single cell can form a colony, and ionizing irradiation has long been known to reduce such a cellular clonogenic potential. Analysis of abortive colonies unable to continue to grow should provide important information on the reproductive cell death (RCD) following irradiation. Our previous analysis with a branching process model showed that the RCD in normal human fibroblasts can persist over 16 generations following irradiation with low linear energy transfer (LET) γ-rays. Here we further set out to evaluate the RCD persistency in abortive colonies arising from normal human fibroblasts exposed to high-LET carbon ions (18.3 MeV/u, 108 keV/µm). We found that the abortive colony size distribution determined by biological experiments follows a linear relationship on the log-log plot, and that the Monte Carlo simulation using the RCD probability estimated from such a linear relationship well simulates the experimentally determined surviving fraction and the relative biological effectiveness (RBE). We identified the short-term phase and long-term phase for the persistent RCD following carbon-ion irradiation, which were similar to those previously identified following γ-irradiation. Taken together, our results suggest that subsequent secondary or tertiary colony formation would be invaluable for understanding the long-lasting RCD. All together, our framework for analysis with a branching process model and a colony formation assay is applicable to determination of cellular responses to low- and high-LET radiation, and suggests that the long-lasting RCD is a pivotal determinant of the surviving fraction and the RBE.
authors: Microbeam Radiation Biology Group, Japan Atomic Energy Agency (JAEA), 1233 Watanuki, Takasaki, Gunma 370-1292, Japan.
authors: Tetsuya
authors: T
authors: Sakashita
authors: Nobuyuki
authors: N
authors: Hamada
authors: Isao
authors: I
authors: Kawaguchi
authors: Takamitsu
authors: T
authors: Hara
authors: Yasuhiko
authors: Y
authors: Kobayashi
authors: Kimiaki
authors: K
authors: Saito
mesh_terms: D002247:Carbon Isotopes / Q000494:pharmacology*; D002449:Cell Aggregation / Q000502:physiology / Q000528:radiation effects; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology / Q000528:radiation effects; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects; D003198:Computer Simulation; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D020450:Heavy Ions; D006801:Humans; D018499:Linear Energy Transfer / Q000502:physiology*; D008954:Models, Biological; D015233:Models, Statistical; D011829:Radiation Dosage; D012062:Relative Biological Effectiveness
chemical_list: D002247:Carbon Isotopes
keywords: branch dynamics; delayed reproductive cell death; ionizing radiation; non-targeted effect