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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2016
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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. |
format | Online Article Text |
id | pubmed-4751252 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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