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Measurement of complex DNA damage induction and repair in human cellular systems after exposure to ionizing radiations of varying linear energy transfer (LET)

Nikitaki, Zacharenia and Nikolov, Vladimir and Mavragani, Ifigeneia V. and Mladenov, Emil and Mangelis, Anastasios and Laskaratou, Danae A. and Fragkoulis, Georgios I. and Hellweg, Christine E. and Martin, Olga A. and Emfietzoglou, Dimitris and Hatzi, Vasiliki I. and Terzoudi, Georgia I. and Iliakis, George and Georgakilas, Alexandros G. (2016) Measurement of complex DNA damage induction and repair in human cellular systems after exposure to ionizing radiations of varying linear energy transfer (LET). Free Radical Research, 50 (sup1), S64-S78. Taylor & Francis. DOI: 10.1080/10715762.2016.1232484 ISSN 1071-5762

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Official URL: http://dx.doi.org/10.1080/10715762.2016.1232484

Abstract

Detrimental effects of ionizing radiation (IR) are correlated to the varying efficiency of IR to induce complex DNA damage. A double strand break (DSB) can be considered the simpler form of complex DNA damage. These types of damage can consist of DSBs, single strand breaks (SSBs) and/or non-DSB lesions such as base damages and apurinic/apyrimidinic (AP; abasic) sites in different combinations. Enthralling theoretical (Monte Carlo simulations) and experimental evidence suggests an increase in the complexity of DNA damage and therefore repair resistance with linear energy transfer (LET). In this study, we have measured the induction and processing of DSB and non-DSB oxidative clusters using adaptations of immunofluorescence. Specifically, we applied foci colocalization approaches as the most current methodologies for the in situ detection of clustered DNA lesions in a variety of human normal (FEP18-11-T1) and cancerous cell lines of varying repair efficiency (MCF7, HepG2, A549, MO59K/J) and radiation qualities of increasing LET, that is γ-, X-rays 0.3–1 keV/μm, α-particles 116 keV/μm and 36Ar ions 270 keV/μm. Using γ-H2AX or 53BP1 foci staining as DSB probes, we calculated a DSB apparent rate of 5–16 DSBs/cell/Gy decreasing with LET. A similar trend was measured for non-DSB oxidized base lesions detected using antibodies against the human repair enzymes 8-oxoguanine-DNA glycosylase (OGG1) or AP endonuclease (APE1), that is damage foci as probes for oxidized purines or abasic sites, respectively. In addition, using colocalization parameters previously introduced by our groups, we detected an increasing clustering of damage for DSBs and non-DSBs. We also make correlations of damage complexity with the repair efficiency of each cell line and we discuss the biological importance of these new findings with regard to the severity of IR due to the complex nature of its DNA damage.

Item URL in elib:https://elib.dlr.de/113067/
Document Type:Article
Title:Measurement of complex DNA damage induction and repair in human cellular systems after exposure to ionizing radiations of varying linear energy transfer (LET)
Authors:
AuthorsInstitution or Email of AuthorsAuthors ORCID iD
Nikitaki, ZachareniaPhysics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Zografou, Athens, GreeceUNSPECIFIED
Nikolov, VladimirInstitute of Medical Radiation Biology, University of Duisburg-Essen Medical School, Essen, GermanyUNSPECIFIED
Mavragani, Ifigeneia V.Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Zografou, Athens, GreeceUNSPECIFIED
Mladenov, EmilInstitute of Medical Radiation Biology, University of Duisburg-Essen Medical School, Essen, GermanyUNSPECIFIED
Mangelis, AnastasiosPhysics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Zografou, Athens, GreeceUNSPECIFIED
Laskaratou, Danae A.Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Zografou, Athens, GreeceUNSPECIFIED
Fragkoulis, Georgios I.Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Zografou, Athens, GreeceUNSPECIFIED
Hellweg, Christine E.Radiation Biology Department, German Aerospace Center (DLR), Institute of Aerospace Medicine, Linder H€ohe, Köln, Germanyhttps://orcid.org/0000-0002-2223-3580
Martin, Olga A.Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia and Sir Peter MacCallum Department of Oncology, The University of Melbourne, Australia and Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, MelbourneUNSPECIFIED
Emfietzoglou, DimitrisMedical Physics Laboratory, Medical School, University of Ioannina, Ioannina, GreeceUNSPECIFIED
Hatzi, Vasiliki I.Laboratory of Health Physics, Radiobiology & Cytogenetics, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research “Demokritos”, Athens, GreeceUNSPECIFIED
Terzoudi, Georgia I.Laboratory of Health Physics, Radiobiology & Cytogenetics, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research “Demokritos”, Athens, GreeceUNSPECIFIED
Iliakis, GeorgeInstitute of Medical Radiation Biology, University of Duisburg-Essen Medical School, Essen, GermanyUNSPECIFIED
Georgakilas, Alexandros G.Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Zografou, Athens, GreeceUNSPECIFIED
Date:2016
Journal or Publication Title:Free Radical Research
Refereed publication:Yes
Open Access:No
Gold Open Access:No
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:50
DOI :10.1080/10715762.2016.1232484
Page Range:S64-S78
Publisher:Taylor & Francis
ISSN:1071-5762
Status:Published
Keywords:Complex DNA damage, non-DSB clusters, foci colocalization, Monte Carlo simulation, high LET ionizing radiations, DNA repair
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Forschung unter Weltraumbedingungen
DLR - Research theme (Project):R - Vorhaben Strahlenbiologie
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Radiation Biology
Deposited By: Kopp, Kerstin
Deposited On:17 Jul 2017 13:24
Last Modified:08 Mar 2018 18:40

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