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Radiat Res. 2019 Jan;191(1):76-92. doi: 10.1667/RR15209.1. Epub 2018 Nov 8.

A New Standard DNA Damage (SDD) Data Format.

Author information

1
a   Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
2
b   Division of Cancer Sciences, The University of Manchester, Manchester, United Kingdom.
3
c   Department of Radiation Oncology, University of California San Francisco, San Francisco, California.
4
d   SLAC National Accelerator Laboratory, Menlo Park, California.
5
e   Medical Research Council, Harwell, United Kingdom.
6
f   KBRwyle, Houston, Texas.
7
g   Physikalisch-Technische Bundesanstalt (PTB), Braunschweig, Germany.
8
h   Task Group 6.2 "Computational Micro- and Nanodosimetry", European Radiation Dosimetry Group e.V., Neuherberg, Germany.
9
i   Institute of Radiation Protection, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
10
j   Physics Department, University of Pavia, Pavia, Italy.
11
k   Department of Physics, East Carolina University, Greenville, North Carolina.
12
l   CNRS, IN2P3, CENBG, UMR 5797, F-33170 Gradignan, France.
13
m   University of Bordeaux, CENBG, UMR 5797, F-33170 Gradignan, France.
14
n   Institut de Radioprotection et Sûreté Nucléaire, F-92262 Fontenay aux Roses Cedex, France.
15
o   Applied Physics Department, Gleb Wataghin Institute of Physics, State University of Campinas, Campinas, SP, Brazil.
16
p   Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW, Australia.
17
q   Department of Radiation Science and Technology, Delft University of Technology, Delft, The Netherlands.
18
r   Department of Physics, Faculty of Science, Saint Joseph University, Beirut, Lebanon.
19
s   Medical Physics Laboratory, University of Ioannina Medical School, Ioannina, Greece.
20
t   Italian National Institute of Nuclear Physics, Section of Pavia, I-27100 Pavia, Italy.
21
u   Department of Radiation Dosimetry, Nuclear Physics Institute of the CAS, Řež, Czech Republic.
22
v   Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
23
w   Health Physics and Diagnostic Sciences, University of Nevada Las Vegas, Las Vegas, Nevada.
24
x   Division of Biomedical Engineering Sciences, School of Medicine, Loma Linda University, Loma Linda, California.
25
y   Department of Radiation Oncology, University of Washington, Seattle, Washington.
26
z   Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut.
27
aa   Medical Radiation Science Group, National Physical Laboratory, Teddington, United Kingdom.
28
bb   School of Physics, University of Sydney, Sydney, NSW, Australia.
29
cc   Institut des Sciences Moléculaires d'Orsay (UMR 8214) University Paris-Sud, CNRS, University Paris-Saclay, 91405 Orsay Cedex, France.
30
dd   Retired.
31
ee   Department of Radiation Physics and Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
32
ff   Department of Accelerator and Medical Physics, National Institute of Radiological Sciences, Chiba, Japan.
33
gg   Japan Atomic Energy Agency, Nuclear Science and Engineering Center, Tokai 319-1196, Japan.
34
hh   Task Group 7.7 "Internal Micro- and Nanodosimetry", European Radiation Dosimetry Group e.V., Neuherberg, Germany.
35
ii   MBN Research Center, 60438 Frankfurt am Main, Germany.
36
jj   Department of Physics, Oakland University, Rochester, Michigan.
37
kk   GSI Helmholtzzentrum für Schwerionenforschung, Biophysics Department, Darmstadt, Germany.
38
ll   Centre for Cancer Research and Cell Biology, Queens University Belfast, Belfast, United Kingdom.

Abstract

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.

PMID:
30407901
PMCID:
PMC6407706
DOI:
10.1667/RR15209.1
[Indexed for MEDLINE]
Free PMC Article

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