Position in proton Bragg curve influences DNA damage complexity and survival in head and neck cancer cells
Background and purpose: Understanding the cellular and molecular effect of proton radiation, particularly the increased DNA damage complexity at the distal end of the Bragg curve, is current topic of investigation. This work aims to study in vitro clonogenic survival and DNA damage foci kinetics of...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Clinical and Translational Radiation Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S240563082400185X |
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| author | Tim Heemskerk Celebrity Groenendijk Marta Rovituso Ernst van der Wal Wouter van Burik Konstantinos Chatzipapas Danny Lathouwers Roland Kanaar Jeremy M.C. Brown Jeroen Essers |
| author_facet | Tim Heemskerk Celebrity Groenendijk Marta Rovituso Ernst van der Wal Wouter van Burik Konstantinos Chatzipapas Danny Lathouwers Roland Kanaar Jeremy M.C. Brown Jeroen Essers |
| author_sort | Tim Heemskerk |
| collection | DOAJ |
| description | Background and purpose: Understanding the cellular and molecular effect of proton radiation, particularly the increased DNA damage complexity at the distal end of the Bragg curve, is current topic of investigation. This work aims to study in vitro clonogenic survival and DNA damage foci kinetics of a head and neck squamous cell carcinoma cell line at various positions along a double passively scattered Bragg curve. Complementary in silico studies are conducted to gain insights into the link between cell survival variations, experimentally yielded foci and the number and complexity of double strand breaks (DSBs). Materials and methods: Proton irradiations are performed at the HollandPTC R&D proton beamline, using a double passively scattered setup. A custom water phantom setup is employed to accurately position the samples within the Bragg curve. FaDu cells are irradiated at the proximal 36 % point of the Bragg peak, (P36), proximal 80 % point of the Bragg peak (P80) and distal 20 % point of the Bragg peak (D20), with dose-averaged mean lineal energies (yD¯) of 1.10 keV/μm, 1.80 keV/μm and 7.25 keV/μm, respectively. Results: Clonogenic survival correlates strongly with yD¯, showing similar survival for P36 (D37%=3.0 Gy) and P80 (D37%=2.9 Gy), but decreased survival for D20 (D37% = 1.6 Gy). D20 irradiated samples exhibit increased 53BP1 foci shortly after irradiation, slower resolution of the foci, and larger residual 53BP1 foci after 24 h, indicating unrepaired complex breaks. These experimental observations are supported by the in silico study which demonstrates that irradiation at D20 leads to a 1.7-fold increase in complex DSBs with respect to the total number of strand breaks compared to P36 and P80. Conclusions: This combined approach provides valuable insights into the cellular and molecular effect of proton radiation, emphasizing the increased DNA damage complexity at the distal end of the Bragg curve, and has the potential to enhance the efficacy of proton therapy. |
| format | Article |
| id | doaj-art-0f98ca26dd7e4e238413079dfe89c383 |
| institution | Kabale University |
| issn | 2405-6308 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Clinical and Translational Radiation Oncology |
| spelling | doaj-art-0f98ca26dd7e4e238413079dfe89c3832025-01-30T05:14:28ZengElsevierClinical and Translational Radiation Oncology2405-63082025-03-0151100908Position in proton Bragg curve influences DNA damage complexity and survival in head and neck cancer cellsTim Heemskerk0Celebrity Groenendijk1Marta Rovituso2Ernst van der Wal3Wouter van Burik4Konstantinos Chatzipapas5Danny Lathouwers6Roland Kanaar7Jeremy M.C. Brown8Jeroen Essers9Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the NetherlandsDepartment of Radiation Science and Technology, Delft University of Technology, Delft, the NetherlandsResearch & Development, HollandPTC, Delft, the NetherlandsResearch & Development, HollandPTC, Delft, the NetherlandsResearch & Development, HollandPTC, Delft, the NetherlandsUniversity of Brest, INSERM, LaTIM, UMR1101, F-29200 Brest, FranceDepartment of Radiation Science and Technology, Delft University of Technology, Delft, the NetherlandsDepartment of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the NetherlandsOptical Sciences Centre, Department of Physics and Astronomy, Swinburne University of Technology, Hawthorn, AustraliaDepartment of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Vascular Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Radiotherapy, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands; Corres ponding author.Background and purpose: Understanding the cellular and molecular effect of proton radiation, particularly the increased DNA damage complexity at the distal end of the Bragg curve, is current topic of investigation. This work aims to study in vitro clonogenic survival and DNA damage foci kinetics of a head and neck squamous cell carcinoma cell line at various positions along a double passively scattered Bragg curve. Complementary in silico studies are conducted to gain insights into the link between cell survival variations, experimentally yielded foci and the number and complexity of double strand breaks (DSBs). Materials and methods: Proton irradiations are performed at the HollandPTC R&D proton beamline, using a double passively scattered setup. A custom water phantom setup is employed to accurately position the samples within the Bragg curve. FaDu cells are irradiated at the proximal 36 % point of the Bragg peak, (P36), proximal 80 % point of the Bragg peak (P80) and distal 20 % point of the Bragg peak (D20), with dose-averaged mean lineal energies (yD¯) of 1.10 keV/μm, 1.80 keV/μm and 7.25 keV/μm, respectively. Results: Clonogenic survival correlates strongly with yD¯, showing similar survival for P36 (D37%=3.0 Gy) and P80 (D37%=2.9 Gy), but decreased survival for D20 (D37% = 1.6 Gy). D20 irradiated samples exhibit increased 53BP1 foci shortly after irradiation, slower resolution of the foci, and larger residual 53BP1 foci after 24 h, indicating unrepaired complex breaks. These experimental observations are supported by the in silico study which demonstrates that irradiation at D20 leads to a 1.7-fold increase in complex DSBs with respect to the total number of strand breaks compared to P36 and P80. Conclusions: This combined approach provides valuable insights into the cellular and molecular effect of proton radiation, emphasizing the increased DNA damage complexity at the distal end of the Bragg curve, and has the potential to enhance the efficacy of proton therapy.http://www.sciencedirect.com/science/article/pii/S240563082400185XProton therapyDNA Breaks, Double-strandedSquamous cell carcinoma of head and neckDNA damageLinear energy transferRadiobiology |
| spellingShingle | Tim Heemskerk Celebrity Groenendijk Marta Rovituso Ernst van der Wal Wouter van Burik Konstantinos Chatzipapas Danny Lathouwers Roland Kanaar Jeremy M.C. Brown Jeroen Essers Position in proton Bragg curve influences DNA damage complexity and survival in head and neck cancer cells Clinical and Translational Radiation Oncology Proton therapy DNA Breaks, Double-stranded Squamous cell carcinoma of head and neck DNA damage Linear energy transfer Radiobiology |
| title | Position in proton Bragg curve influences DNA damage complexity and survival in head and neck cancer cells |
| title_full | Position in proton Bragg curve influences DNA damage complexity and survival in head and neck cancer cells |
| title_fullStr | Position in proton Bragg curve influences DNA damage complexity and survival in head and neck cancer cells |
| title_full_unstemmed | Position in proton Bragg curve influences DNA damage complexity and survival in head and neck cancer cells |
| title_short | Position in proton Bragg curve influences DNA damage complexity and survival in head and neck cancer cells |
| title_sort | position in proton bragg curve influences dna damage complexity and survival in head and neck cancer cells |
| topic | Proton therapy DNA Breaks, Double-stranded Squamous cell carcinoma of head and neck DNA damage Linear energy transfer Radiobiology |
| url | http://www.sciencedirect.com/science/article/pii/S240563082400185X |
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