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Modeling the Effect of Hypoxia and DNA Repair Inhibition on Cell Survival after Photon Irradiation

Mechanistic approaches to modeling the effects of ionizing radiation on cells are on the rise, promising a better understanding of predictions and higher flexibility concerning conditions to be accounted for. In this work we modified and extended a previously published mechanistic model of cell surv...

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Autores principales: Liew, Hans, Klein, Carmen, Zenke, Frank T., Abdollahi, Amir, Debus, Jürgen, Dokic, Ivana, Mairani, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929106/
https://www.ncbi.nlm.nih.gov/pubmed/31801300
http://dx.doi.org/10.3390/ijms20236054
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author Liew, Hans
Klein, Carmen
Zenke, Frank T.
Abdollahi, Amir
Debus, Jürgen
Dokic, Ivana
Mairani, Andrea
author_facet Liew, Hans
Klein, Carmen
Zenke, Frank T.
Abdollahi, Amir
Debus, Jürgen
Dokic, Ivana
Mairani, Andrea
author_sort Liew, Hans
collection PubMed
description Mechanistic approaches to modeling the effects of ionizing radiation on cells are on the rise, promising a better understanding of predictions and higher flexibility concerning conditions to be accounted for. In this work we modified and extended a previously published mechanistic model of cell survival after photon irradiation under hypoxia to account for radiosensitization caused by deficiency or inhibition of DNA damage repair enzymes. The model is shown to be capable of describing the survival data of cells with DNA damage repair deficiency, both under norm- and hypoxia. We find that our parameterization of radiosensitization is invariant under change of oxygen status, indicating that the relevant parameters for both mechanisms can be obtained independently and introduced freely to the model to predict their combined effect.
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spelling pubmed-69291062019-12-26 Modeling the Effect of Hypoxia and DNA Repair Inhibition on Cell Survival after Photon Irradiation Liew, Hans Klein, Carmen Zenke, Frank T. Abdollahi, Amir Debus, Jürgen Dokic, Ivana Mairani, Andrea Int J Mol Sci Article Mechanistic approaches to modeling the effects of ionizing radiation on cells are on the rise, promising a better understanding of predictions and higher flexibility concerning conditions to be accounted for. In this work we modified and extended a previously published mechanistic model of cell survival after photon irradiation under hypoxia to account for radiosensitization caused by deficiency or inhibition of DNA damage repair enzymes. The model is shown to be capable of describing the survival data of cells with DNA damage repair deficiency, both under norm- and hypoxia. We find that our parameterization of radiosensitization is invariant under change of oxygen status, indicating that the relevant parameters for both mechanisms can be obtained independently and introduced freely to the model to predict their combined effect. MDPI 2019-11-30 /pmc/articles/PMC6929106/ /pubmed/31801300 http://dx.doi.org/10.3390/ijms20236054 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liew, Hans
Klein, Carmen
Zenke, Frank T.
Abdollahi, Amir
Debus, Jürgen
Dokic, Ivana
Mairani, Andrea
Modeling the Effect of Hypoxia and DNA Repair Inhibition on Cell Survival after Photon Irradiation
title Modeling the Effect of Hypoxia and DNA Repair Inhibition on Cell Survival after Photon Irradiation
title_full Modeling the Effect of Hypoxia and DNA Repair Inhibition on Cell Survival after Photon Irradiation
title_fullStr Modeling the Effect of Hypoxia and DNA Repair Inhibition on Cell Survival after Photon Irradiation
title_full_unstemmed Modeling the Effect of Hypoxia and DNA Repair Inhibition on Cell Survival after Photon Irradiation
title_short Modeling the Effect of Hypoxia and DNA Repair Inhibition on Cell Survival after Photon Irradiation
title_sort modeling the effect of hypoxia and dna repair inhibition on cell survival after photon irradiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929106/
https://www.ncbi.nlm.nih.gov/pubmed/31801300
http://dx.doi.org/10.3390/ijms20236054
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