Abstract
A mechanistic model of cellular survival following radiation-induced DNA double-strand breaks (DSBs) was proposed in this study. DSBs were assumed as the initial lesions in the DNA of the cell nucleus induced by ionizing radiation. The non-homologous end-joining (NHEJ) pathway was considered as the domain pathway of DSB repair in mammalian cells. The model was proposed to predict the relationship between radiation-induced DSBs in nucleus and probability of cell survival, which was quantitatively described by two input parameters and six fitting parameters. One input parameter was the average number of primary particles which caused DSB, the other input parameter was the average number of DSBs yielded by each primary particle that caused DSB. The fitting parameters were used to describe the biological characteristics of the irradiated cells. By determining the fitting parameters of the model with experimental data, the model is able to estimate surviving fractions for the same type of cells exposed to particles with different physical parameters. The model further revealed the mechanism of cell death induced by the DSB effect. Relative biological effectiveness (RBE) of charged particles at different survival could be calculated with the model, which would provide reference for clinical treatment.
Highlights
The target theory was the initial exploration of the relationship between energy deposition in cells and probability of cell survival, which was of great significance for later theories
The mechanistic models include the repair-misrepair-fixation (RMF) model proposed by Stewart et al.[26], the biophysical analysis of cell death and chromosome aberrations (BIANCA) model proposed by Ballarini et al.[27,28,29], the mechanistic modelling of DNA repair and cellular survival following radiation-induced DNA damage proposed by Stephen et al.[30,31], etc
The input parameters of the model are the average number of primary particles which caused double-strand breaks (DSBs) and the average number of DSBs yielded by each primary particle that caused DSB
Summary
The target theory was the initial exploration of the relationship between energy deposition in cells and probability of cell survival, which was of great significance for later theories. For improving descriptions of high dose survival responses, different models have been proposed, such as the Padé Linear Quadratic (PLQ) model[4,5,6], the Universal Survival Curve (USC) model[7] and the Linear-Quadratic-Linear (LQL) model[8], which were proved to be theoretically well-founded and useful in clinical applications at high doses as well as medium and low doses[9] These models are phenomenological models, which are in good agreement with experimental data. As experimental studies only allow to calculate cell survival for specific irradiation conditions, a number of models have been proposed to predict cell survival for mixed beams with the concept of relative biological effectiveness (RBE) of protons and carbon ions to photons[12]. To characterize cellular response towards ionizing irradiation at the molecular and cellular level, such as radiation-induced DNA damage, DNA damage repair, chromosome aberration formation and consequent cell death, several mechanistic models have been proposed too. With the fitting parameters obtained from experimental data, the model allows to estimate surviving fractions for the same type of cell exposed to different particles at different linear energy transfer (LET)
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