A branching process model for the analysis of abortive colony size distributions in carbon ion-irradiated normal human fibroblasts

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. © 2013 the author. published by oxford university press on behalf of the japan radiation research society and japanese society for radiation oncology.