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Variations in the Processing of DNA Double-Strand Breaks Along 60-MeV Therapeutic Proton Beams

PURPOSE: To investigate the variations in induction and repair of DNA damage along the proton path, after a previous report on the increasing biological effectiveness along clinically modulated 60-MeV proton beams. METHODS AND MATERIALS: Human skin fibroblast (AG01522) cells were irradiated along a...

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Autores principales: Chaudhary, Pankaj, Marshall, Thomas I., Currell, Frederick J., Kacperek, Andrzej, Schettino, Giuseppe, Prise, Kevin M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science Inc 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840231/
https://www.ncbi.nlm.nih.gov/pubmed/26452569
http://dx.doi.org/10.1016/j.ijrobp.2015.07.2279
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author Chaudhary, Pankaj
Marshall, Thomas I.
Currell, Frederick J.
Kacperek, Andrzej
Schettino, Giuseppe
Prise, Kevin M.
author_facet Chaudhary, Pankaj
Marshall, Thomas I.
Currell, Frederick J.
Kacperek, Andrzej
Schettino, Giuseppe
Prise, Kevin M.
author_sort Chaudhary, Pankaj
collection PubMed
description PURPOSE: To investigate the variations in induction and repair of DNA damage along the proton path, after a previous report on the increasing biological effectiveness along clinically modulated 60-MeV proton beams. METHODS AND MATERIALS: Human skin fibroblast (AG01522) cells were irradiated along a monoenergetic and a modulated spread-out Bragg peak (SOBP) proton beam used for treating ocular melanoma at the Douglas Cyclotron, Clatterbridge Centre for Oncology, Wirral, Liverpool, United Kingdom. The DNA damage response was studied using the 53BP1 foci formation assay. The linear energy transfer (LET) dependence was studied by irradiating the cells at depths corresponding to entrance, proximal, middle, and distal positions of SOBP and the entrance and peak position for the pristine beam. RESULTS: A significant amount of persistent foci was observed at the distal end of the SOBP, suggesting complex residual DNA double-strand break damage induction corresponding to the highest LET values achievable by modulated proton beams. Unlike the directly irradiated, medium-sharing bystander cells did not show any significant increase in residual foci. CONCLUSIONS: The DNA damage response along the proton beam path was similar to the response of X rays, confirming the low-LET quality of the proton exposure. However, at the distal end of SOBP our data indicate an increased complexity of DNA lesions and slower repair kinetics. A lack of significant induction of 53BP1 foci in the bystander cells suggests a minor role of cell signaling for DNA damage under these conditions.
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spelling pubmed-48402312016-05-02 Variations in the Processing of DNA Double-Strand Breaks Along 60-MeV Therapeutic Proton Beams Chaudhary, Pankaj Marshall, Thomas I. Currell, Frederick J. Kacperek, Andrzej Schettino, Giuseppe Prise, Kevin M. Int J Radiat Oncol Biol Phys RBE and Particle Therapy Biology PURPOSE: To investigate the variations in induction and repair of DNA damage along the proton path, after a previous report on the increasing biological effectiveness along clinically modulated 60-MeV proton beams. METHODS AND MATERIALS: Human skin fibroblast (AG01522) cells were irradiated along a monoenergetic and a modulated spread-out Bragg peak (SOBP) proton beam used for treating ocular melanoma at the Douglas Cyclotron, Clatterbridge Centre for Oncology, Wirral, Liverpool, United Kingdom. The DNA damage response was studied using the 53BP1 foci formation assay. The linear energy transfer (LET) dependence was studied by irradiating the cells at depths corresponding to entrance, proximal, middle, and distal positions of SOBP and the entrance and peak position for the pristine beam. RESULTS: A significant amount of persistent foci was observed at the distal end of the SOBP, suggesting complex residual DNA double-strand break damage induction corresponding to the highest LET values achievable by modulated proton beams. Unlike the directly irradiated, medium-sharing bystander cells did not show any significant increase in residual foci. CONCLUSIONS: The DNA damage response along the proton beam path was similar to the response of X rays, confirming the low-LET quality of the proton exposure. However, at the distal end of SOBP our data indicate an increased complexity of DNA lesions and slower repair kinetics. A lack of significant induction of 53BP1 foci in the bystander cells suggests a minor role of cell signaling for DNA damage under these conditions. Elsevier Science Inc 2016-05-01 /pmc/articles/PMC4840231/ /pubmed/26452569 http://dx.doi.org/10.1016/j.ijrobp.2015.07.2279 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle RBE and Particle Therapy Biology
Chaudhary, Pankaj
Marshall, Thomas I.
Currell, Frederick J.
Kacperek, Andrzej
Schettino, Giuseppe
Prise, Kevin M.
Variations in the Processing of DNA Double-Strand Breaks Along 60-MeV Therapeutic Proton Beams
title Variations in the Processing of DNA Double-Strand Breaks Along 60-MeV Therapeutic Proton Beams
title_full Variations in the Processing of DNA Double-Strand Breaks Along 60-MeV Therapeutic Proton Beams
title_fullStr Variations in the Processing of DNA Double-Strand Breaks Along 60-MeV Therapeutic Proton Beams
title_full_unstemmed Variations in the Processing of DNA Double-Strand Breaks Along 60-MeV Therapeutic Proton Beams
title_short Variations in the Processing of DNA Double-Strand Breaks Along 60-MeV Therapeutic Proton Beams
title_sort variations in the processing of dna double-strand breaks along 60-mev therapeutic proton beams
topic RBE and Particle Therapy Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840231/
https://www.ncbi.nlm.nih.gov/pubmed/26452569
http://dx.doi.org/10.1016/j.ijrobp.2015.07.2279
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