Radiation dose rate effects: what is new and what is needed?

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.

Section: Patterns Of Radiation-induced Dna Damage: Interactions At Di...mentioning

confidence: 99%

“…dose rate and dose fractionation effects and their interplay with radiation quality. The issue of dose rate effects is separately addressed by a different article (Lowe et al 2022).…”

Section: Introductionmentioning

confidence: 99%

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

Baiocco

Bartzsch

Conte

et al. 2022

“…In the case of low indoor radon exposures, where individual cellular energy deposition events are widely spaced in time, the temporal distribution of energy deposition events, and hence dose rate, will affect the resulting biological response, which may be accounted for by the dose and dose rate effectiveness factor (DDREF, for review see Lowe et al 2022). If an already hit cell in bronchial epithelium is hit again by an alpha particle after about 30 days, which is the average lifetime of lungs cells (Adamson 1985), then the initial DNA damage in that cell may have already been repaired or that cell may have been replaced by a new cell by division or apoptosis.…”

Section: Priorities For New Research Activitiesmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Madas

Boei

Fenske

et al. 2022

Exposure to radon progeny results in heterogeneous dose distributions in many different spatial scales. 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 and its association with lung cancer, along with priorities for future research. Particular attention is paid on the effects of spatial variation in dose delivery within the organs, a factor not considered in radiation protection. It is concluded that a multidisciplinary approach is required to improve risk assessment and mechanistic understanding of carcinogenesis related to radon exposure. To achieve these goals, important steps would be to clarify whether radon can cause other diseases than lung cancer, and to investigate radon-related health risks in children or persons at young ages. Also, a better understanding of the combined effects of radon and smoking is needed, which can be achieved by integrating epidemiological, clinical, pathological, and molecular oncology data to obtain a radon-associated signature. While in vitro models derived from primary human bronchial epithelial cells can help to identify new and corroborate existing biomarkers, they also allow to study the effects of heterogeneous dose distributions including the effects of locally high doses. These novel approaches can provide valuable input and validation data for mathematical models for risk assessment. These models can be applied to quantitatively translate the knowledge obtained from radon exposure to other exposures resulting in heterogeneous dose distributions within an organ to support radiation protection in general.

“…With a focus on low LET radiation exposure and dose rates relevant for radiological protection, Lowe et al (2022) presented a comprehensive assessment of radiation dose rate studies to date, including molecular, cellular, animal, and human studies with very informative tables on the exposed biological systems, the irradiation details, the recorded outcomes, definitive findings and references. Limits and advantages of each approach were discussed.…”

mentioning

confidence: 99%

The 2020 MELODI workshop on the effects of spatial and temporal variation in dose delivery

Madas

Wójcik

2022

A key activity of MELODI is to organise annual European meetings where scientific results and future directions and strategies of relevant research are discussed. The annual meetings, previously organised solely under the auspices of MELODI are, since 2016, jointly organised by the European platforms and referred to as European Radiation Protection Weeks (ERPW). In addition to ERPW meetings, MELODI organises and finances annual workshops dedicated to specific topics. Outputs and recommendations from the meetings are published as review articles. The 2020 workshop focussed on one of the cross cutting topics: the effects of spatial and temporal variation in dose delivery on disease risk. The current issue of REBS includes five review articles from the workshop on the effects of spatial and temporal variation in dose delivery and this editorial is a short summary of their content.