Abstract
Biological responses to ionizing radiation (IR) have been studied for many years, generally showing the dependence of these responses on the quality of radiation, i.e., the radiation particle type and energy, types of DNA damage, dose and dose rate, type of cells, etc. There is accumulating evidence on the pivotal role of complex (clustered) DNA damage towards the determination of the final biological or even clinical outcome after exposure to IR. In this review, we provide literature evidence about the significant role of damage clustering and advancements that have been made through the years in its detection and prediction using Monte Carlo (MC) simulations. We conclude that in the future, emphasis should be given to a better understanding of the mechanistic links between the induction of complex DNA damage, its processing, and systemic effects at the organism level, like genomic instability and immune responses.
Highlights
Ionizing radiation (IR) is considered to be an environmental or anthropogenic genotoxic agent and has a varying quality depending on its type, i.e., electromagnetic or particles, etc
Than carbon ions, which are heavier, is attributed to the fact that the latter are accelerated in order to be used in therapy, while the linear energy transfer (LET) of alpha particles refers to their production by spontaneous emission taking place during alpha decay
The signaling and repair of complex DNA damage, induced by high-LET IR is coordinated through the specific induction of H2Bub catalyzed by MSL2 and RNF20/40, a mechanism that contributes to decreased cell survival after irradiation
Summary
Ionizing radiation (IR) is considered to be an environmental or anthropogenic genotoxic agent and has a varying quality depending on its type, i.e., electromagnetic or particles, etc. In order to explain various radiobiological findings, several empirical deterministic models have been developed so far, contributing to the interpretation of the general trend of the experimental data These models provide satisfactory qualitative results at relatively high doses, they cannot always contribute efficiently to corresponding outcomes at low doses [33]. Other models, such as the local effect model (LEM) [35] and the microdosimetric kinetic model (MKM) [36], take into account the LET and other quality characteristics of the irradiating particles and the tracks of the secondary particles in the calculation of the cell survival curves Besides these models, the BIANCA model, in addition to cell survival, predicts chromosome aberrations, which can be regarded as a strong indicator of normal tissue damage [3,37]
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