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...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-07-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02635-1 |
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| author | Maria Rita Fabbrizi Jonathan R. Hughes Leah D. Punshon Laura Hawkins Vasily Sorokin Alice Ormrod Emma Melia Karthik Vaidya Carlos P. Rubbi Ben Phoenix Mark A. Hill Jason L. Parsons |
| author_facet | Maria Rita Fabbrizi Jonathan R. Hughes Leah D. Punshon Laura Hawkins Vasily Sorokin Alice Ormrod Emma Melia Karthik Vaidya Carlos P. Rubbi Ben Phoenix Mark A. Hill Jason L. Parsons |
| author_sort | Maria Rita Fabbrizi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ca4941ebb3c94be3a6a5cbb45193a0d4 |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-ca4941ebb3c94be3a6a5cbb45193a0d42025-08-20T03:42:47ZengNature Publishing GroupCell Death Discovery2058-77162025-07-011111810.1038/s41420-025-02635-1Radiobiological characterisation of a 28 MeV proton beam delivered by the MC-40 cyclotronMaria Rita Fabbrizi0Jonathan R. Hughes1Leah D. Punshon2Laura Hawkins3Vasily Sorokin4Alice Ormrod5Emma Melia6Karthik Vaidya7Carlos P. Rubbi8Ben Phoenix9Mark A. Hill10Jason L. Parsons11Department of Cancer and Genomic Sciences, University of Birmingham, EdgbastonDepartment of Cancer and Genomic Sciences, University of Birmingham, EdgbastonDepartment of Cancer and Genomic Sciences, University of Birmingham, EdgbastonDepartment of Cancer and Genomic Sciences, University of Birmingham, EdgbastonOxford Institute for Radiation Oncology, University of Oxford, Gray Laboratories, ORCRB Roosevelt DriveDepartment of Cancer and Genomic Sciences, University of Birmingham, EdgbastonDepartment of Cancer and Genomic Sciences, University of Birmingham, EdgbastonDepartment of Cancer and Genomic Sciences, University of Birmingham, EdgbastonMedical School, Edge Hill University, St Helens RoadSchool of Physics and Astronomy, University of Birmingham, EdgbastonOxford Institute for Radiation Oncology, University of Oxford, Gray Laboratories, ORCRB Roosevelt DriveDepartment of Cancer and Genomic Sciences, University of Birmingham, EdgbastonAbstract 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.https://doi.org/10.1038/s41420-025-02635-1 |
| spellingShingle | Maria Rita Fabbrizi Jonathan R. Hughes Leah D. Punshon Laura Hawkins Vasily Sorokin Alice Ormrod Emma Melia Karthik Vaidya Carlos P. Rubbi Ben Phoenix Mark A. Hill Jason L. Parsons Radiobiological characterisation of a 28 MeV proton beam delivered by the MC-40 cyclotron Cell Death Discovery |
| title | Radiobiological characterisation of a 28 MeV proton beam delivered by the MC-40 cyclotron |
| title_full | Radiobiological characterisation of a 28 MeV proton beam delivered by the MC-40 cyclotron |
| title_fullStr | Radiobiological characterisation of a 28 MeV proton beam delivered by the MC-40 cyclotron |
| title_full_unstemmed | Radiobiological characterisation of a 28 MeV proton beam delivered by the MC-40 cyclotron |
| title_short | Radiobiological characterisation of a 28 MeV proton beam delivered by the MC-40 cyclotron |
| title_sort | radiobiological characterisation of a 28 mev proton beam delivered by the mc 40 cyclotron |
| url | https://doi.org/10.1038/s41420-025-02635-1 |
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