RESEARCH ARTICLE Model Assembly for Estimating Cell Surviving Fraction for Both Targeted and Nontargeted Effects Based on Microdosimetric Probability Densities

We here propose a new model assembly for estimating the surviving fraction of cells irradiated with various types of ionizing radiation, considering both targeted and nontargeted effects in the same framework. The probability densities of specific energies in two scales, which are the cell nucleus and its substructure called a domain, were employed as the physical index for characterizing the radiation fields. In the model assembly, our previously established double stochastic microdosimetric kinetic (DSMK) model was used to express the targeted effect, whereas a newly developed model was used to express the nontargeted effect. The radioresistance caused by overexpression of anti-apoptotic protein Bcl-2 known to frequently occur in human cancer was also considered by introducing the concept of the adaptive response in the DSMK model. The accuracy of the model assembly was examined by comparing the computationally and experimentally determined surviving fraction of Bcl-2 cells (Bcl-2 overexpressing HeLa cells) and Neo cells (neomycin resistant gene-expressing HeLa cells) irradiated with microbeam o