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DNA Damage Responses following Exposure to Modulated Radiation Fields

During the delivery of advanced radiotherapy treatment techniques modulated beams are utilised to increase dose conformity across the target volume. Recent investigations have highlighted differential cellular responses to modulated radiation fields particularly in areas outside the primary treatmen...

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Autores principales: Trainor, Colman, Butterworth, Karl T., McGarry, Conor K., McMahon, Stephen J., O’Sullivan, Joe M., Hounsell, Alan R., Prise, Kevin M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422245/
https://www.ncbi.nlm.nih.gov/pubmed/22912853
http://dx.doi.org/10.1371/journal.pone.0043326
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author Trainor, Colman
Butterworth, Karl T.
McGarry, Conor K.
McMahon, Stephen J.
O’Sullivan, Joe M.
Hounsell, Alan R.
Prise, Kevin M.
author_facet Trainor, Colman
Butterworth, Karl T.
McGarry, Conor K.
McMahon, Stephen J.
O’Sullivan, Joe M.
Hounsell, Alan R.
Prise, Kevin M.
author_sort Trainor, Colman
collection PubMed
description During the delivery of advanced radiotherapy treatment techniques modulated beams are utilised to increase dose conformity across the target volume. Recent investigations have highlighted differential cellular responses to modulated radiation fields particularly in areas outside the primary treatment field that cannot be accounted for by scattered dose alone. In the present study, we determined the DNA damage response within the normal human fibroblast AG0-1522B and the prostate cancer cell line DU-145 utilising the DNA damage assay. Cells plated in slide flasks were exposed to 1 Gy uniform or modulated radiation fields. Modulated fields were delivered by shielding 25%, 50% or 75% of the flask during irradiation. The average number of 53BP1 or γH2AX foci was measured in 2 mm intervals across the slide area. Following 30 minutes after modulated radiation field exposure an increase in the average number of foci out-of-field was observed when compared to non-irradiated controls. In-field, a non-uniform response was observed with a significant decrease in the average number of foci compared to uniformly irradiated cells. Following 24 hrs after exposure there is evidence for two populations of responding cells to bystander signals in-and out-of-field. There was no significant difference in DNA damage response between 25%, 50% or 75% modulated fields. The response was dependent on cellular secreted intercellular signalling as physical inhibition of intercellular communication abrogated the observed response. Elevated residual DNA damage observed within out-of-field regions decreased following addition of an inducible nitric oxide synthase inhibitor (Aminoguanidine). These data show, for the first time, differential DNA damage responses in-and out-of-field following modulated radiation field delivery. This study provides further evidence for a role of intercellular communication in mediating cellular radiobiological response to modulated radiation fields and may inform the refinement of existing radiobiological models for the optimization of advanced radiotherapy treatment plans.
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spelling pubmed-34222452012-08-21 DNA Damage Responses following Exposure to Modulated Radiation Fields Trainor, Colman Butterworth, Karl T. McGarry, Conor K. McMahon, Stephen J. O’Sullivan, Joe M. Hounsell, Alan R. Prise, Kevin M. PLoS One Research Article During the delivery of advanced radiotherapy treatment techniques modulated beams are utilised to increase dose conformity across the target volume. Recent investigations have highlighted differential cellular responses to modulated radiation fields particularly in areas outside the primary treatment field that cannot be accounted for by scattered dose alone. In the present study, we determined the DNA damage response within the normal human fibroblast AG0-1522B and the prostate cancer cell line DU-145 utilising the DNA damage assay. Cells plated in slide flasks were exposed to 1 Gy uniform or modulated radiation fields. Modulated fields were delivered by shielding 25%, 50% or 75% of the flask during irradiation. The average number of 53BP1 or γH2AX foci was measured in 2 mm intervals across the slide area. Following 30 minutes after modulated radiation field exposure an increase in the average number of foci out-of-field was observed when compared to non-irradiated controls. In-field, a non-uniform response was observed with a significant decrease in the average number of foci compared to uniformly irradiated cells. Following 24 hrs after exposure there is evidence for two populations of responding cells to bystander signals in-and out-of-field. There was no significant difference in DNA damage response between 25%, 50% or 75% modulated fields. The response was dependent on cellular secreted intercellular signalling as physical inhibition of intercellular communication abrogated the observed response. Elevated residual DNA damage observed within out-of-field regions decreased following addition of an inducible nitric oxide synthase inhibitor (Aminoguanidine). These data show, for the first time, differential DNA damage responses in-and out-of-field following modulated radiation field delivery. This study provides further evidence for a role of intercellular communication in mediating cellular radiobiological response to modulated radiation fields and may inform the refinement of existing radiobiological models for the optimization of advanced radiotherapy treatment plans. Public Library of Science 2012-08-17 /pmc/articles/PMC3422245/ /pubmed/22912853 http://dx.doi.org/10.1371/journal.pone.0043326 Text en © 2012 Trainor 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
Trainor, Colman
Butterworth, Karl T.
McGarry, Conor K.
McMahon, Stephen J.
O’Sullivan, Joe M.
Hounsell, Alan R.
Prise, Kevin M.
DNA Damage Responses following Exposure to Modulated Radiation Fields
title DNA Damage Responses following Exposure to Modulated Radiation Fields
title_full DNA Damage Responses following Exposure to Modulated Radiation Fields
title_fullStr DNA Damage Responses following Exposure to Modulated Radiation Fields
title_full_unstemmed DNA Damage Responses following Exposure to Modulated Radiation Fields
title_short DNA Damage Responses following Exposure to Modulated Radiation Fields
title_sort dna damage responses following exposure to modulated radiation fields
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422245/
https://www.ncbi.nlm.nih.gov/pubmed/22912853
http://dx.doi.org/10.1371/journal.pone.0043326
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