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The Biological Effect of Large Single Doses: A Possible Role for Non-Targeted Effects in Cell Inactivation

BACKGROUND AND PURPOSE: Novel radiotherapy techniques increasingly use very large dose fractions. It has been argued that the biological effect of large dose fractions may differ from that of conventional fraction sizes. The purpose was to study the biological effect of large single doses. MATERIAL...

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Autores principales: Veldwijk, Marlon R., Zhang, Bo, Wenz, Frederik, Herskind, Carsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898915/
https://www.ncbi.nlm.nih.gov/pubmed/24465461
http://dx.doi.org/10.1371/journal.pone.0084991
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author Veldwijk, Marlon R.
Zhang, Bo
Wenz, Frederik
Herskind, Carsten
author_facet Veldwijk, Marlon R.
Zhang, Bo
Wenz, Frederik
Herskind, Carsten
author_sort Veldwijk, Marlon R.
collection PubMed
description BACKGROUND AND PURPOSE: Novel radiotherapy techniques increasingly use very large dose fractions. It has been argued that the biological effect of large dose fractions may differ from that of conventional fraction sizes. The purpose was to study the biological effect of large single doses. MATERIAL AND METHODS: Clonogenic cell survival of MCF7 and MDA-MB-231 cells was determined after direct X-ray irradiation, irradiation of feeder cells, or transfer of conditioned medium (CM). Cell-cycle distributions and the apoptotic sub-G1 fraction were measured by flow cytometry. Cytokines in CM were quantified by a cytokine antibody array. γH2AX foci were detected by immunofluorescence microscopy. RESULTS: The surviving fraction of MCF7 cells irradiated in vitro with 12 Gy showed an 8.5-fold decrease (95% c.i.: 4.4–16.3; P<0.0001) when the density of irradiated cells was increased from 10 to 50×10(3) cells per flask. Part of this effect was due to a dose-dependent transferrable factor as shown in CM experiments in the dose range 5–15 Gy. While no effect on apoptosis and cell cycle distribution was observed, and no differentially expressed cytokine could be identified, the transferable factor induced prolonged expression of γH2AX DNA repair foci at 1–12 h. CONCLUSIONS: A dose-dependent non-targeted effect on clonogenic cell survival was found in the dose range 5–15 Gy. The dependence of SF on cell numbers at high doses would represent a “cohort effect” in vivo. These results support the hypothesis that non-targeted effects may contribute to the efficacy of very large dose fractions in radiotherapy.
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spelling pubmed-38989152014-01-24 The Biological Effect of Large Single Doses: A Possible Role for Non-Targeted Effects in Cell Inactivation Veldwijk, Marlon R. Zhang, Bo Wenz, Frederik Herskind, Carsten PLoS One Research Article BACKGROUND AND PURPOSE: Novel radiotherapy techniques increasingly use very large dose fractions. It has been argued that the biological effect of large dose fractions may differ from that of conventional fraction sizes. The purpose was to study the biological effect of large single doses. MATERIAL AND METHODS: Clonogenic cell survival of MCF7 and MDA-MB-231 cells was determined after direct X-ray irradiation, irradiation of feeder cells, or transfer of conditioned medium (CM). Cell-cycle distributions and the apoptotic sub-G1 fraction were measured by flow cytometry. Cytokines in CM were quantified by a cytokine antibody array. γH2AX foci were detected by immunofluorescence microscopy. RESULTS: The surviving fraction of MCF7 cells irradiated in vitro with 12 Gy showed an 8.5-fold decrease (95% c.i.: 4.4–16.3; P<0.0001) when the density of irradiated cells was increased from 10 to 50×10(3) cells per flask. Part of this effect was due to a dose-dependent transferrable factor as shown in CM experiments in the dose range 5–15 Gy. While no effect on apoptosis and cell cycle distribution was observed, and no differentially expressed cytokine could be identified, the transferable factor induced prolonged expression of γH2AX DNA repair foci at 1–12 h. CONCLUSIONS: A dose-dependent non-targeted effect on clonogenic cell survival was found in the dose range 5–15 Gy. The dependence of SF on cell numbers at high doses would represent a “cohort effect” in vivo. These results support the hypothesis that non-targeted effects may contribute to the efficacy of very large dose fractions in radiotherapy. Public Library of Science 2014-01-22 /pmc/articles/PMC3898915/ /pubmed/24465461 http://dx.doi.org/10.1371/journal.pone.0084991 Text en © 2014 Veldwijk et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Veldwijk, Marlon R.
Zhang, Bo
Wenz, Frederik
Herskind, Carsten
The Biological Effect of Large Single Doses: A Possible Role for Non-Targeted Effects in Cell Inactivation
title The Biological Effect of Large Single Doses: A Possible Role for Non-Targeted Effects in Cell Inactivation
title_full The Biological Effect of Large Single Doses: A Possible Role for Non-Targeted Effects in Cell Inactivation
title_fullStr The Biological Effect of Large Single Doses: A Possible Role for Non-Targeted Effects in Cell Inactivation
title_full_unstemmed The Biological Effect of Large Single Doses: A Possible Role for Non-Targeted Effects in Cell Inactivation
title_short The Biological Effect of Large Single Doses: A Possible Role for Non-Targeted Effects in Cell Inactivation
title_sort biological effect of large single doses: a possible role for non-targeted effects in cell inactivation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898915/
https://www.ncbi.nlm.nih.gov/pubmed/24465461
http://dx.doi.org/10.1371/journal.pone.0084991
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