Development of a DNA damage model that accommodates different cellular oxygen concentrations and radiation qualities

Research regarding cellular responses at different oxygen concentrations (OCs) is of immense interest within the field of radiobiology. Therefore, this study aimed to develop a mechanistic model to analyze cellular responses at different OCs.

A DNA damage model (the different cell oxygen level DNA damage [DICOLDD] model) that examines the oxygen effect was developed based on the oxygen fixation hypothesis, which states that dissolved oxygen can modify the reaction kinetics of DNA-derived radicals generated by ionizing radiation. The generation of DNA-derived radicals was simulated using the Monte Carlo method. The decay of DNA-derived radicals due to the competing processes of chemical repair, oxygen fixation, and intrinsic damaging was described using differential equations. The DICOLDD model was fitted to the previous experimental data obtained under different irradiation configurations and validated by calculating the yields of DNA double-strand breaks (DSBs) after exposure to ¹³⁷ Cs as well as cell survival fractions (SFs) using a mechanistic model of cellular survival. Moreover, we used the DICOLDD model to calculate DNA DSB damage yields after irradiation with 0.5-50 MeV protons.

Generally, DSB yields calculated after exposure to ¹³⁷ Cs at different OCs correspond to statistical uncertainties of previous experimental results. Calculated SFs of CHO and V79 cells exposed to photons, protons, and alpha particles at different OCs generally concur with those obtained in previous studies. Our results demonstrated that the variation in DSB yields was less than 10% when the cellular OC decreased from 21% to 5%. Additionally, DSB yields changed drastically when OC dropped below 1%.

We developed a DNA damage model to evaluate the oxygen effect and provide evidence that a reaction-kinetic model of DNA-derived radicals induced by ionizing radiation suffices to explain the observed oxygen effects. Therefore, the DICOLDD model is a powerful tool for the analysis of cellular responses at different OCs after exposure to different types of radiation.