ArticleThe British journal of radiology2025
FLASH-induced DNA damage reduction measured in vitro correlates with effective oxygen depletion determined in silico: further support for oxygen depletion contributing to FLASH's reduced damage burden in vitro.
Article in The British journal of radiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Harnessing the sparing effect of FLASH-RT: From phenomenon observation, radiophysical determinants to molecular mechanisms and synergistic strategies.Materials today. Bio · 2026Review
- Oxygen Depletion in FLASH Particle Therapy: Effects of Linear Energy Transfer and Ion Track Structure.Antioxidants (Basel, Switzerland) · 2026Article
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Authors and funding
9 authors.
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Abstract
objectivesFLASH irradiation demonstrates notable normal-tissue protective effects, including reduced damage in vitro. Radiochemical mechanisms proposed include radical-radical recombination and transient oxygen depletion (TOD), but the relative contributions remain unclear. This study compares FLASH-mediated DNA damage reduction in vitro with oxygen depletion for FLASH radiotherapy modelled in silico, to (i) investigate the contribution of TOD towards the reduced damage burden in vitro, and (ii) evaluate its contribution to the broader FLASH effect in vivo.
methodsAn in silico model was used to identify and compare the parameter space for FLASH-induced oxygen depletion in an in-vitro setup with experimental DNA damage reduction data, previously determined using the alkaline comet assay ex vivo.
resultsCorrelation analysis revealed a strong relationship between model-predicted oxygen depletion and experimentally-observed DNA damage reduction (Spearman's = 0.87, P = 2 × 10-6; Pearson's = 0.85, P = 4 × 10-6).
conclusionsFindings support a significant role for TOD in the FLASH-induced reduction in damage in vitro at low oxygen tensions. However, parameter spaces identified, for both oxygen depletion in silico and DNA damage reduction in vitro, suggest that TOD may only partially contribute to the wider-ranging FLASH sparing effects in vivo. Further work is required to clarify this. ADVANCES IN KNOWLEDGE: Findings support TOD as a key mechanism for the reduced damage burden of FLASH in vitro. However, further work is required to demarcate the sparing effects of FLASH in vivo.
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