A matter of space: how the spatial heterogeneity in energy deposition determines the biological outcome of radiation exposure

Abstract

The outcome of the exposure of living organisms to ionizing radiation is determined by the distribution of the associated energy deposition at different spatial scales. Radiation proceeds through ionizations and excitations of hit molecules with an ~ nm spacing. Approaches such as nanodosimetry/microdosimetry and Monte Carlo track-structure simulations have been successfully adopted to investigate radiation quality effects: they allow to explore correlations between the spatial clustering of such energy depositions at the scales of DNA or chromosome domains and their biological consequences at the cellular level. Physical features alone, however, are not enough to assess the entity and complexity of radiation-induced DNA damage: this latter is the result of an interplay between radiation track structure and the spatial architecture of chromatin, and further depends on the chromatin dynamic response, affecting the activation and efficiency of the repair machinery. The heterogeneity of radiation energy depositions at the single-cell level affects the trade-off between cell inactivation and induction of viable mutations and hence influences radiation-induced carcinogenesis. In radiation therapy, where the goal is cancer cell inactivation, the delivery of a homogenous dose to the tumour has been the traditional approach in clinical practice. However, evidence is accumulating that introducing heterogeneity with spatially fractionated beams (mini- and microbeam therapy) can lead to significant advantages, particularly in sparing normal tissues. Such findings cannot be explained in merely physical terms, and their interpretation requires considering the scales at play in the underlying biological mechanisms, suggesting a systemic response to radiation.

Out-of-field effects: lessons learned from partial body exposure

“…The MELODI Workshop 2020 on the “Spatial and temporal variation in dose delivery” brought together experts in clinical/epidemiological/dosimetric and biological/mechanistic aspects of research. It was organized in four sessions, addressing (1) dose-rate effects, (2) radiation quality, (3) internal exposure and (4) partial body exposure, each generating at least one thematic manuscript (Lowe et al 2022 ; Baiocco et al 2022 ; Boei et al 2022 ; Li et al 2022 ). Due to COVID19 outbreak, the workshop was successfully held on-line.…”

Integrating microdosimetric in vitro RBE models for particle therapy into TOPAS MC using the MicrOdosimetry-based modeliNg for RBE ASsessment (MONAS) tool

“…Notably, (Conte et al 2018, Selva et al 2020, nanodosimetry offers a direct pathway to understanding the biological consequences of radiation exposure. Furthermore, it has become evident that both microdosimetric and nanodosimetric scales play a significant role in assessing radiation-induced biological damage (Friedrich et al 2018, Baiocco et al 2022. However, it is crucial to highlight that accurately simulating nanoscale phenomena necessitates the implementation of a physics list based on track structure, which, for the sake of clarity, is not the focus of this paper.…”

Effects of spatial variation in dose delivery: what can we learn from radon-related lung cancer studies?

“…The aim of this review is to provide an overview on the state of the art in epidemiology, clinical observations, cell biology, dosimetry, and modelling related to radon exposure along with priorities for future research. As the effects of spatial heterogeneity in energy deposition (Baiocco et al 2022), partial body exposures (Pazzaglia et al 2022), and dose rate (Lowe et al 2022) are covered in other papers of this theme issue, particular attention is paid here on the effects of spatial variation in dose delivery in the lungs upon radon exposure, a factor not considered in radiation protection (Madas 2016a).…”