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Efficient Rejoining of DNA Double-Strand Breaks despite Increased Cell-Killing Effectiveness following Spread-Out Bragg Peak Carbon-Ion Irradiation

Radiotherapy of solid tumors with charged particles holds several advantages in comparison to photon therapy; among them conformal dose distribution in the tumor, improved sparing of tumor-surrounding healthy tissue, and an increased relative biological effectiveness (RBE) in the tumor target volume...

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Autores principales: Averbeck, Nicole B., Topsch, Jana, Scholz, Michael, Kraft-Weyrather, Wilma, Durante, Marco, Taucher-Scholz, Gisela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751252/
https://www.ncbi.nlm.nih.gov/pubmed/26904506
http://dx.doi.org/10.3389/fonc.2016.00028
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author Averbeck, Nicole B.
Topsch, Jana
Scholz, Michael
Kraft-Weyrather, Wilma
Durante, Marco
Taucher-Scholz, Gisela
author_facet Averbeck, Nicole B.
Topsch, Jana
Scholz, Michael
Kraft-Weyrather, Wilma
Durante, Marco
Taucher-Scholz, Gisela
author_sort Averbeck, Nicole B.
collection PubMed
description Radiotherapy of solid tumors with charged particles holds several advantages in comparison to photon therapy; among them conformal dose distribution in the tumor, improved sparing of tumor-surrounding healthy tissue, and an increased relative biological effectiveness (RBE) in the tumor target volume in the case of ions heavier than protons. A crucial factor of the biological effects is DNA damage, of which DNA double-strand breaks (DSBs) are the most deleterious. The reparability of these lesions determines the cell survival after irradiation and thus the RBE. Interestingly, using phosphorylated H2AX as a DSB marker, our data in human fibroblasts revealed that after therapy-relevant spread-out Bragg peak irradiation with carbon ions DSBs are very efficiently rejoined, despite an increased RBE for cell survival. This suggests that misrepair plays an important role in the increased RBE of heavy-ion radiation. Possible sources of erroneous repair will be discussed.
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spelling pubmed-47512522016-02-22 Efficient Rejoining of DNA Double-Strand Breaks despite Increased Cell-Killing Effectiveness following Spread-Out Bragg Peak Carbon-Ion Irradiation Averbeck, Nicole B. Topsch, Jana Scholz, Michael Kraft-Weyrather, Wilma Durante, Marco Taucher-Scholz, Gisela Front Oncol Oncology Radiotherapy of solid tumors with charged particles holds several advantages in comparison to photon therapy; among them conformal dose distribution in the tumor, improved sparing of tumor-surrounding healthy tissue, and an increased relative biological effectiveness (RBE) in the tumor target volume in the case of ions heavier than protons. A crucial factor of the biological effects is DNA damage, of which DNA double-strand breaks (DSBs) are the most deleterious. The reparability of these lesions determines the cell survival after irradiation and thus the RBE. Interestingly, using phosphorylated H2AX as a DSB marker, our data in human fibroblasts revealed that after therapy-relevant spread-out Bragg peak irradiation with carbon ions DSBs are very efficiently rejoined, despite an increased RBE for cell survival. This suggests that misrepair plays an important role in the increased RBE of heavy-ion radiation. Possible sources of erroneous repair will be discussed. Frontiers Media S.A. 2016-02-12 /pmc/articles/PMC4751252/ /pubmed/26904506 http://dx.doi.org/10.3389/fonc.2016.00028 Text en Copyright © 2016 Averbeck, Topsch, Scholz, Kraft-Weyrather, Durante and Taucher-Scholz. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Averbeck, Nicole B.
Topsch, Jana
Scholz, Michael
Kraft-Weyrather, Wilma
Durante, Marco
Taucher-Scholz, Gisela
Efficient Rejoining of DNA Double-Strand Breaks despite Increased Cell-Killing Effectiveness following Spread-Out Bragg Peak Carbon-Ion Irradiation
title Efficient Rejoining of DNA Double-Strand Breaks despite Increased Cell-Killing Effectiveness following Spread-Out Bragg Peak Carbon-Ion Irradiation
title_full Efficient Rejoining of DNA Double-Strand Breaks despite Increased Cell-Killing Effectiveness following Spread-Out Bragg Peak Carbon-Ion Irradiation
title_fullStr Efficient Rejoining of DNA Double-Strand Breaks despite Increased Cell-Killing Effectiveness following Spread-Out Bragg Peak Carbon-Ion Irradiation
title_full_unstemmed Efficient Rejoining of DNA Double-Strand Breaks despite Increased Cell-Killing Effectiveness following Spread-Out Bragg Peak Carbon-Ion Irradiation
title_short Efficient Rejoining of DNA Double-Strand Breaks despite Increased Cell-Killing Effectiveness following Spread-Out Bragg Peak Carbon-Ion Irradiation
title_sort efficient rejoining of dna double-strand breaks despite increased cell-killing effectiveness following spread-out bragg peak carbon-ion irradiation
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751252/
https://www.ncbi.nlm.nih.gov/pubmed/26904506
http://dx.doi.org/10.3389/fonc.2016.00028
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