TOPAS-nBio: Modeling effects of radiation with nanometer-scale Monte Carlo simulations*

The Monte Carlo (MC) method has been successfully employed to simulate radiotherapy down to the cellular scale. In order to understand how energy deposition within irradiated cells (physics) connects via molecular reactions (chemistry) to cell kill/repair (biology), one has to understand how damage and repair of cellular components is linked to frequencies of energy depositions in sub-cellular targets such as DNA.
MC simulation offers a unique tool to explore these effects. To make this method more accessible we developed TOPAS-nBio, a nanometer scale extension for radiobiology to the TOPAS MC system layered on top of the Geant4/Geant4-DNA MC toolkit. TOPAS-nBio includes detailed cell geometries, such as various DNA models, mitochondria and cells (e.g. fibroblasts or neurons). Two implementations of chemistry can be used with up to 72 reactions classified into 6 types between neutral and charged species. We reproduced time-dependent G-values within 7% for ^●OH and e^-_aq and 50% for H₂O₂ as well as DNA damage in plasmids within 50%. The physical and chemical simulations depict direct and indirect damages to cells which are propagated using mechanistic models of DNA repair kinetics.