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A New Standard DNA Damage (SDD) Data Format

J. Schuemann, AL. McNamara, JW. Warmenhoven, NT. Henthorn, KJ. Kirkby, MJ. Merchant, S. Ingram, H. Paganetti, KD. Held, J. Ramos-Mendez, B. Faddegon, J. Perl, DT. Goodhead, I. Plante, H. Rabus, H. Nettelbeck, W. Friedland, P. Kundrát, A....

. 2019 ; 191 (1) : 76-92. [pub] 20181108

Language English Country United States

Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't

Grant support
R01 CA187003 NCI NIH HHS - United States

Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called "indirect" damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.

b Division of Cancer Sciences The University of Manchester Manchester United Kingdom

bb School of Physics University of Sydney Sydney NSW Australia

c Department of Radiation Oncology University of California San Francisco San Francisco California

cc Institut des Sciences Moléculaires d'Orsay University Paris Sud CNRS University Paris Saclay 91405 Orsay Cedex France

Department of Radiation Oncology Massachusetts General Hospital and Harvard Medical School Boston Massachusetts

e Medical Research Council Harwell United Kingdom

ee Department of Radiation Physics and Imaging Physics The University of Texas MD Anderson Cancer Center Houston Texas

f KBRwyle Houston Texas

ff Department of Accelerator and Medical Physics National Institute of Radiological Sciences Chiba Japan

g Physikalisch Technische Bundesanstalt Braunschweig Germany h Task Group 6 2 Computational Micro and Nanodosimetry European Radiation Dosimetry Group e 5 Neuherberg Germany

gg Japan Atomic Energy Agency Nuclear Science and Engineering Center Tokai 319 1196 Japan

h Task Group 6 2 Computational Micro and Nanodosimetry European Radiation Dosimetry Group e 5 Neuherberg Germany i Institute of Radiation Protection Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany

h Task Group 6 2 Computational Micro and Nanodosimetry European Radiation Dosimetry Group e 5 Neuherberg Germany j Physics Department University of Pavia Pavia Italy

h Task Group 6 2 Computational Micro and Nanodosimetry European Radiation Dosimetry Group e 5 Neuherberg Germany n Institut de Radioprotection et Sûreté Nucléaire F 92262 Fontenay aux Roses Cedex France

i Institute of Radiation Protection Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany

i Institute of Radiation Protection Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany hh Task Group 7 7 Internal Micro and Nanodosimetry European Radiation Dosimetry Group e 5 Neuherberg Germany

ii MBN Research Center 60438 Frankfurt am Main Germany

Institut de Radioprotection et Sûreté Nucléaire F 92262 Fontenay aux Roses Cedex France

j Physics Department University of Pavia Pavia Italy

j Physics Department University of Pavia Pavia Italy t Italian National Institute of Nuclear Physics Section of Pavia 1 27100 Pavia Italy

jj Department of Physics Oakland University Rochester Michigan

k Department of Physics East Carolina University Greenville North Carolina

kk GSI Helmholtzzentrum für Schwerionenforschung Biophysics Department Darmstadt Germany

l CNRS IN2P3 CENBG UMR 5797 F 33170 Gradignan France

l CNRS IN2P3 CENBG UMR 5797 F 33170 Gradignan France m University of Bordeaux CENBG UMR 5797 F 33170 Gradignan France

ll Centre for Cancer Research and Cell Biology Queens University Belfast Belfast United Kingdom

Medical Radiation Science Group National Physical Laboratory Teddington United Kingdom

o Applied Physics Department Gleb Wataghin Institute of Physics State University of Campinas Campinas SP Brazil

p Centre for Medical Radiation Physics University of Wollongong Wollongong NSW Australia

q Department of Radiation Science and Technology Delft University of Technology Delft The Netherlands

r Department of Physics Faculty of Science Saint Joseph University Beirut Lebanon

Retired

s Medical Physics Laboratory University of Ioannina Medical School Ioannina Greece

SLAC National Accelerator Laboratory Menlo Park California

u Department of Radiation Dosimetry Nuclear Physics Institute of the CAS Řež Czech Republic

v Department of Radiation Oncology University of Texas Southwestern Medical Center Dallas Texas

w Health Physics and Diagnostic Sciences University of Nevada Las Vegas Las Vegas Nevada

x Division of Biomedical Engineering Sciences School of Medicine Loma Linda University Loma Linda California

y Department of Radiation Oncology University of Washington Seattle Washington

z Department of Therapeutic Radiology Yale University School of Medicine New Haven Connecticut

References provided by Crossref.org

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$a A New Standard DNA Damage (SDD) Data Format / $c J. Schuemann, AL. McNamara, JW. Warmenhoven, NT. Henthorn, KJ. Kirkby, MJ. Merchant, S. Ingram, H. Paganetti, KD. Held, J. Ramos-Mendez, B. Faddegon, J. Perl, DT. Goodhead, I. Plante, H. Rabus, H. Nettelbeck, W. Friedland, P. Kundrát, A. Ottolenghi, G. Baiocco, S. Barbieri, M. Dingfelder, S. Incerti, C. Villagrasa, M. Bueno, MA. Bernal, S. Guatelli, D. Sakata, JMC. Brown, Z. Francis, I. Kyriakou, N. Lampe, F. Ballarini, MP. Carante, M. Davídková, V. Štěpán, X. Jia, FA. Cucinotta, R. Schulte, RD. Stewart, DJ. Carlson, S. Galer, Z. Kuncic, S. Lacombe, J. Milligan, SH. Cho, G. Sawakuchi, T. Inaniwa, T. Sato, W. Li, AV. Solov'yov, E. Surdutovich, M. Durante, KM. Prise, SJ. McMahon,
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$a Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called "indirect" damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.
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