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

Giorgio Baiocco, Stefan Bartzsch, Valeria Conte, Thomas Friedrich, Burkhard Jakob, Adrianna Tartas, Carmen Villagrasa, Kevin M Prise

Research output: Contribution to journalReview articlepeer-review

18 Citations (Scopus)
24 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)545-559
Number of pages15
JournalRadiation and Environmental Biophysics
Volume61
Issue number4
Early online date12 Oct 2022
DOIs
Publication statusPublished - 01 Nov 2022

Bibliographical note

© 2022. The Author(s).

Keywords

  • Chromatin
  • DNA Damage
  • DNA damage and repair
  • Ionizing Radiation
  • Micro- And Nanodosimetry
  • Monte Carlo Method
  • Radiation Exposure
  • Radiation Track Structure
  • Radiation, Ionizing
  • Spatially Fractionated Radiation Therapy
  • relative biological effectiveness

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