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Mathematical modelling of the automated FADU assay for the quantification of DNA strand breaks and their repair in human peripheral mononuclear blood cells

BACKGROUND: Cells continuously undergo DNA damage from exogenous agents like irradiation or genotoxic chemicals or from endogenous radicals produced by normal cellular metabolic activities. DNA strand breaks are one of the most common genotoxic lesions and they can also arise as intermediates of DNA...

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Autores principales: Junk, Michael, Salzwedel, Judy, Sindlinger, Thilo, Bürkle, Alexander, Moreno-Villanueva, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470348/
https://www.ncbi.nlm.nih.gov/pubmed/26085926
http://dx.doi.org/10.1186/s13628-014-0009-z
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author Junk, Michael
Salzwedel, Judy
Sindlinger, Thilo
Bürkle, Alexander
Moreno-Villanueva, Maria
author_facet Junk, Michael
Salzwedel, Judy
Sindlinger, Thilo
Bürkle, Alexander
Moreno-Villanueva, Maria
author_sort Junk, Michael
collection PubMed
description BACKGROUND: Cells continuously undergo DNA damage from exogenous agents like irradiation or genotoxic chemicals or from endogenous radicals produced by normal cellular metabolic activities. DNA strand breaks are one of the most common genotoxic lesions and they can also arise as intermediates of DNA repair activity. Unrepaired DNA damage can lead to genomic instability, which can massively compromise the health status of organisms. Therefore it is important to measure and quantify DNA damage and its repair. RESULTS: We have previously published an automated method for measuring DNA strand breaks based on fluorimetric detection of alkaline DNA unwinding [1], and here we present a mathematical model of the FADU assay, which enables to an analytic expression for the relation between measured fluorescence and the number of strand breaks. CONCLUSIONS: Assessment of the formation and also the repair of DNA strand breaks is a crucial functional parameter to investigate genotoxicity in living cells. A reliable and convenient method to quantify DNA strand breakage is therefore of significant importance for a wide variety of scientific fields, e.g. toxicology, pharmacology, epidemiology and medical sciences.
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spelling pubmed-44703482015-06-18 Mathematical modelling of the automated FADU assay for the quantification of DNA strand breaks and their repair in human peripheral mononuclear blood cells Junk, Michael Salzwedel, Judy Sindlinger, Thilo Bürkle, Alexander Moreno-Villanueva, Maria BMC Biophys Methodology Article BACKGROUND: Cells continuously undergo DNA damage from exogenous agents like irradiation or genotoxic chemicals or from endogenous radicals produced by normal cellular metabolic activities. DNA strand breaks are one of the most common genotoxic lesions and they can also arise as intermediates of DNA repair activity. Unrepaired DNA damage can lead to genomic instability, which can massively compromise the health status of organisms. Therefore it is important to measure and quantify DNA damage and its repair. RESULTS: We have previously published an automated method for measuring DNA strand breaks based on fluorimetric detection of alkaline DNA unwinding [1], and here we present a mathematical model of the FADU assay, which enables to an analytic expression for the relation between measured fluorescence and the number of strand breaks. CONCLUSIONS: Assessment of the formation and also the repair of DNA strand breaks is a crucial functional parameter to investigate genotoxicity in living cells. A reliable and convenient method to quantify DNA strand breakage is therefore of significant importance for a wide variety of scientific fields, e.g. toxicology, pharmacology, epidemiology and medical sciences. BioMed Central 2014-09-09 /pmc/articles/PMC4470348/ /pubmed/26085926 http://dx.doi.org/10.1186/s13628-014-0009-z Text en Copyright © 2014 Junk et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Methodology Article
Junk, Michael
Salzwedel, Judy
Sindlinger, Thilo
Bürkle, Alexander
Moreno-Villanueva, Maria
Mathematical modelling of the automated FADU assay for the quantification of DNA strand breaks and their repair in human peripheral mononuclear blood cells
title Mathematical modelling of the automated FADU assay for the quantification of DNA strand breaks and their repair in human peripheral mononuclear blood cells
title_full Mathematical modelling of the automated FADU assay for the quantification of DNA strand breaks and their repair in human peripheral mononuclear blood cells
title_fullStr Mathematical modelling of the automated FADU assay for the quantification of DNA strand breaks and their repair in human peripheral mononuclear blood cells
title_full_unstemmed Mathematical modelling of the automated FADU assay for the quantification of DNA strand breaks and their repair in human peripheral mononuclear blood cells
title_short Mathematical modelling of the automated FADU assay for the quantification of DNA strand breaks and their repair in human peripheral mononuclear blood cells
title_sort mathematical modelling of the automated fadu assay for the quantification of dna strand breaks and their repair in human peripheral mononuclear blood cells
topic Methodology Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470348/
https://www.ncbi.nlm.nih.gov/pubmed/26085926
http://dx.doi.org/10.1186/s13628-014-0009-z
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