Journal article
Radiobiological characterisation of a 28 MeV proton beam delivered by the MC-40 cyclotron
- Abstract:
- Proton beam therapy (PBT) is a targeted radiotherapy treatment that can deliver the majority of the radiation dose to the tumour being treated via the Bragg peak. However, there is biological and clinical uncertainty of PBT due to the increases in linear energy transfer (LET) at and around the Bragg peak. Through radiobiological characterisation of a 28 MeV pristine proton beam at several positions relative to the Bragg peak, we demonstrate that there are decreases in survival of head and neck squamous cell carcinoma (HNSCC) and HeLa cells relative to increasing LET. Through monitoring DNA damage using γH2AX/53BP1/OGG1 foci via immunofluorescence microscopy and different versions of the comet assay, we show that increasing relative biological effectiveness (RBE) is directly associated with predominantly DNA single strand breaks that were more difficult to repair and persisted, in addition to a strong correlation with increases in the presence of more persistent complex DNA damage. Increasing frequencies of micronuclei as a marker of chromosomal damage were also observed as a function of LET. Our data demonstrate that increases in LET across the Bragg peak can create changes in the DNA damage spectrum that drive the radiobiological response.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.0MB, Terms of use)
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- Publisher copy:
- 10.1038/s41420-025-02635-1
Authors
+ Medical Research Council
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- Funder identifier:
- https://ror.org/03x94j517
- Grant:
- MR/V028944
+ National Institutes of Health
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- Funder identifier:
- https://ror.org/01cwqze88
- Grant:
- 1R01CA256854-01
- Publisher:
- Springer Nature
- Journal:
- Cell Death Discovery More from this journal
- Volume:
- 11
- Issue:
- 1
- Article number:
- 334
- Publication date:
- 2025-07-21
- Acceptance date:
- 2025-07-08
- DOI:
- EISSN:
-
2058-7716
- Language:
-
English
- Pubs id:
-
2247370
- Local pid:
-
pubs:2247370
- Deposit date:
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2025-07-21
- ARK identifier:
Terms of use
- Copyright holder:
- Fabbrizi et al.
- Copyright date:
- 2025
- Rights statement:
- © The Author(s) 2025. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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