DNA damage complexity as a predictor of cell survival: a microscopic Monte Carlo-based modeling framework for photon, proton and carbon ion irradiation

OBJECTIVE: Biological effect of charged particles characterized by cell surviving fraction (SF) depends on physical factors such as particle type, dose, beam quality descriptors, e.g. linear energy transfer (LET) or lineal energy. Driven by the crucial role of DNA double-strand breaks (DSBs) as indicators of cellular responses to ionizing radiation, this study aims to develop a cell-specific SF model based on the initial DSBs of varying complexities universal with respect to photon, proton, and carbon-ion irradiations across different beam qualities. Approach: Microscopic Monte Carlo simulations (MMCSs) were used to calculate DSBs for experiments measuring SF of H460 and H1437 lung cancer cells irradiated by proton (dose-mean lineal energy y ̅_d 2.0-20.0 keV/ µm), carbon ions (y ̅_d 18.6-87.9 keV/µm) and reference 137Cs photon beam. We modeled SF as a third-order polynomial function of DSBs of various complexities with two, three, and more strand breaks. The function was determined by a data fitting process. Main results: For each cell line, a single model was able to accurately describe SF in experiments under all 19 irradiation conditions with different particle types and y ̅_d values. Root Mean Square Errors were 0.218 for H460 cells and 0.170 for H1437 cells. When applying the model to a proton spread-out-Bragg-peak case, calculated relative biological effectiveness at SF=0.1 were 1.01-1.42 for the H460 cells and 1.03-1.65 for the H1437 cells depending on the depth. Significance: We successfully developed a SF model using DSBs of various complexities as input variables. The model is universally applicable to photon, proton, and carbon-ion irradiations across different beam qualities. .