Rapid MCNP simulation of DNA double strand break (DSB) relative biological effectiveness (RBE) for photons, neutrons, and light ions
Open accessAbstract
To account for particle interactions in the extracellular (physical) environment, information from the cell-level Monte Carlo damage simulation (MCDS) for DNA double strand break (DSB) induction has been integrated into the general purpose Monte Carlo N-particle (MCNP) radiation transport code system. The effort to integrate these models is motivated by the need for a computationally efficient model to accurately predict particle relative biological effectiveness (RBE) in cell cultures and in vivo . To illustrate the approach and highlight the impact of the larger scale physical environment (e.g. establishing charged particle equilibrium), we examined the RBE for DSB induction (RBE DSB ) of x-rays, 137 Cs γ -rays, neutrons and light ions relative to γ -rays from 60 Co in monolayer cell cultures at various depths in water. Under normoxic conditions, we found that 137 Cs γ -rays are about 1.7% more effective at creating DSB than γ -rays from 60 Co (RBE DSB = 1.017) whereas 60–250 kV x-rays are 1.1 to 1.25 times more efficient at creating DSB than 60 Co. Under anoxic conditions, kV x-rays may have an RBE DSB up to 1.51 times as large as 60 Co γ -rays. Fission neutrons passing through monolayer cell cultures have an RBE DSB that ranges from 2.6 to 3.0 in normoxic cells, but may be as large as 9.93 for anoxic cells. For proton pencil beams, Monte Carlo simulations suggest an RBE DSB of about 1.2 at the tip of the Bragg peak and up to 1.6 a few mm beyond the Bragg peak. Bragg peak RBE DSB increases with decreasing oxygen concentration, which may create opportunities to apply proton dose painting to help address tumor hypoxia. Modeling of the particle RBE for DSB induction across multiple physical and biological scales has the potential to aid in the interpretation of laboratory experiments and provide useful information to advance the safety and effectiveness of hadron therapy in the treatment of cancer.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The RBE model here presented for clustered DNA damage induction is the first fully based on ab-initio calculations starting from physical interactions.
“and the one here presented for clustered DNA damage induction is the first fully based on ab-initio calculations starting from physical interactions.”
From The origin of neutron biological effectiveness as a function of energy (2016) · cites this paper as [20]
The Introduction describes this paper’s RBE formulas as empirical fits to MCDS estimates, not as fully ab-initio calculations. The section “Relationship of the MCDS to track structure simulations of DNA damage” says the MCDS places lesions indirectly using parameters, while describing earlier track-structure simulations that begin with physical particle interactions. This contradicts both the claimed basis of this model and its claimed priority. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredFew RBE models for neutrons exist all together, from older applications to neutron therapy up to recent neutron RBE for DNA damage induction.
“To our knowledge few RBE models for neutrons exist all together, from older applications to neutron therapy1819 up to recent neutron RBE for DNA damage induction20”
From The origin of neutron biological effectiveness as a function of energy (2016) · cites this paper as [20]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 85 · Cited by 103
Research works printed but not linked: 49
- Alloni D, Campa A, Belli M, Esposito G, Facoetti A, Friedland W, Liotta M, Mariotti L, Paretzke H G and Ottolenghi A 2010 A Monte Carlo study of the radiation quality dependence of DNA fragmentation spectra Radiat. Res. 173 263-71 · DOI
- Alloni D, Campa A, Friedland W, Mariotti L and Ottolenghi A 2013 Integration of Monte Carlo simulations with PFGE experimental data yields constant RBE of 2.3 for DNA double-strand break induction by nitrogen ions between 125 and 225 keV/mum LET Radiat. Res. 179 690-7 · DOI
- Anderson M E and Bond W H 1963 Neutron spectrum of a plutonium-beryllium source Nucl. Phys. 43 330-8 · DOI
- Averbeck N B, Ringel O, Herrlitz M, Jakob B, Durante M and Taucher-Scholz G 2014 DNA end resection is needed for the repair of complex lesions in G1-phase human cells Cell Cycle 13 2509-16 · DOI
- Ballarini F, Biaggi M, Merzagora M, Ottolenghi A, Dingfelder M, Friedland W, Jacob P and Paretzke H G 2000 Stochastic aspects and uncertainties in the prechemical and chemical stages of electron tracks in liquid water: a quantitative analysis based on Monte Carlo simulations Radiat. Environ. Biophys. 39 179-88 · DOI
- Bedford J S 1991 Sublethal damage, potentially lethal damage, and chromosomal aberrations in mammalian cells exposed to ionizing radiations Int. J. Radiat. Oncol. Biol. Phys. 21 1457-69 · DOI
- Bernhardt P, Friedland W, Meckbach R, Jacob P and Paretzke H G 2002 Monte Carlo simulation of DNA damage by low LET radiation using inhomogeneous higher order DNA targets Radiat. Prot. Dosim. 99 203-6 · DOI
- Burigo L, Pshenichnov I, Mishustin I and Bleicher M 2015 Comparative study of dose distributions and cell survival fractions for 1H, 4He, 12C and 16O beams using Geant4 and Microdosimetric Kinetic model Phys. Med. Biol. 60 3313-31 · DOI
- Byrne M, Wray J, Reinert B, Wu Y, Nickoloff J, Lee S H, Hromas R and Williamson E 2014 Mechanisms of oncogenic chromosomal translocations Ann. NY Acad. Sci. 1310 89-97 · DOI
- Campa A et al 2005 DNA DSB induced in human cells by charged particles and gamma rays: experimental results and theoretical approaches Int. J. Radiat. Biol. 81 841-54 · DOI
- Campa A et al 2009 DNA fragmentation induced in human fibroblasts by 56Fe ions: experimental data and Monte Carlo simulations Radiat. Res. 171 438-45 · DOI · Paper page
- Carlson D J, Stewart R D, Semenenko V A and Sandison G A 2008 Combined use of Monte Carlo DNA damage simulations and deterministic repair models to examine putative mechanisms of cell killing Radiat. Res. 169 447-59 · DOI
- Caswell R S 1966 Deposition of energy by neutrons in spherical cavities Radiat. Res. 27 92-107 · DOI
- Cornforth M N and Bedford J S 1987 A quantitative comparison of potentially lethal damage repair and the rejoining of interphase chromosome breaks in low passage normal human fibroblasts Radiat. Res. 111 385-405 · DOI
- Curtis S B 1986 Lethal and potentially lethal lesions induced by radiation-a unified repair model Radiat. Res. 106 252-70 · DOI
- Czub J et al 2008 Biological effectiveness of (12)C and (20)Ne ions with very high LET Int. J. Radiat. Biol. 84 821-9 · DOI
- Ezzati A O, Xiao Y, Sohrabpour M and Studenski M T 2015 The effect of energy spectrum change on DNA damage in and out of field in 10 MV clinical photon beams Med. Biol. Eng. Comput. 53 67-75 · DOI
- Flynn R T, Bowen S R, Bentzen S M, Rockwell Mackie T and Jeraj R 2008 Intensity-modulated x-ray (IMXT) versus proton (IMPT) therapy for theragnostic hypoxia-based dose painting Phys. Med. Biol. 53 4153-67 · DOI
- Frankenberg-Schwager M, Gebauer A, Koppe C, Wolf H, Pralle E and Frankenberg D 2009 Single- strand annealing, conservative homologous recombination, nonhomologous DNA end joining, and the cell cycle-dependent repair of DNA double-strand breaks induced by sparsely or densely ionizing radiation Radiat. Res. 171 265-73 · DOI
- Frese M C, Yu V K, Stewart R D and Carlson D J 2012 A mechanism-based approach to predict the relative biological effectiveness of protons and carbon ions in radiation therapy Int. J. Radiat. Oncol. Biol. Phys. 83 442-50 · DOI
- Friedland W, Bernhardt P, Jacob P, Paretzke H G and Dingfelder M 2002 Simulation of DNA damage after proton and low LET irradiation Radiat. Prot. Dosim. 99 99-102 · DOI
- Friedland W, Dingfelder M, Jacob P and Paretzke H G 2005 Calculated DNA double-strand break and fragmentation yields after irradiation with He ions Radiat. Phys. Chem. 72 279-86 · DOI
- Friedland W, Jacob P, Bernhardt P, Paretzke H G and Dingfelder M 2003 Simulation of DNA damage after proton irradiation Radiat. Res. 159 401-10 · DOI
- Friedrich T, Durante M and Scholz M 2012a Modeling cell survival after photon irradiation based on double-strand break clustering in megabase pair chromatin loops Radiat. Res. 178 385-94 · DOI
- Friedrich T, Scholz U, Elsasser T, Durante M and Scholz M 2012b Calculation of the biological effects of ion beams based on the microscopic spatial damage distribution pattern Int. J. Radiat. Biol. 88 103-7 · DOI
- Furusawa Y, Fukutsu K, Aoki M, Itsukaichi H, Eguchi-Kasai K, Ohara H, Yatagai F, Kanai T and Ando K 2000 Inactivation of aerobic and hypoxic cells from three different cell lines by accelerated (3)He-, (12)C-and (20)Ne-ion beams Radiat. Res. 154 485-96 · DOI
- Georgakilas A G, O'Neill P and Stewart R D 2013 Induction and repair of clustered DNA lesions: what do we know so far? Radiat. Res. 180 100-9 · DOI · Paper page
- Goodhead D T 1994 Initial events in the cellular effects of ionizing radiations: clustered damage in DNA Int. J. Radiat. Biol. 65 7-17 · DOI · Paper page
- Hawkins R B 1998 A microdosimetric-kinetic theory of the dependence of the RBE for cell death on LET Med. Phys. 25 1157-70 · DOI
- Hawkins R B 2003 A microdosimetric-kinetic model for the effect of non-Poisson distribution of lethal lesions on the variation of RBE with LET Radiat. Res. 160 61-9 · DOI
- Hawkins R B 2009 The relationship between the sensitivity of cells to high-energy photons and the RBE of particle radiation used in radiotherapy Radiat. Res. 172 761-76 · DOI
- Hlatky L, Sachs R K, Vazquez M and Cornforth M N 2002 Radiation-induced chromosome aberrations: insights gained from biophysical modeling Bioessays 24 714-23 · DOI
- Holley W R and Chatterjee A 1996 Clusters of DNA induced by ionizing radiation: formation of short DNA fragments: I. Theoretical modeling Radiat. Res. 145 188-99 · DOI
- Hsiao Y Y, Hung T H, Tu S J and Tung C J 2014 Fast Monte Carlo simulation of DNA damage induction by Auger-electron emission Int. J. Radiat. Biol. 90 392-400 · DOI
- Hsiao Y and Stewart R D 2008 Monte Carlo simulation of DNA damage induction by x-rays and selected radioisotopes Phys. Med. Biol. 53 233-44 ICRU 1983 Microdosimetry (Bethesda: International Commission of Radiation Units and Measurements) International Organization for Standardization 1989 Neutron Reference Radiations for Calibrating As a Function of Neutron Energy, International Standard ISO-8529 · DOI
- Jeggo P A 2002 The fidelity of repair of radiation damage Radiat. Prot. Dosim. 99 117-22 · DOI
- Kamp F C G, Mairani A, Parodi K, Wilkens J J and Carlson D J 2015 Fast biological modeling for voxel- based heavy ion therapy treatment planning using the mechanistic repair-misrepair-fixation (RMF) model and nuclear fragment spectra Int. J. Radiat. Oncol. Biol. Phys. 93 557-68 · DOI
- Kirkby C, Ghasroddashti E, Poirier Y, Tambasco M and Stewart R D 2013 RBE of kV CBCT radiation determined by Monte Carlo DNA damage simulations Phys. Med. Biol. 58 5693-704 · DOI
- Kreipl M S, Friedland W and Paretzke H G 2009 Interaction of ion tracks in spatial and temporal proximity Radiat. Environ. Biophys. 48 349-59 · DOI
- Mairani A, Brons S, Cerutti F, Fasso A, Ferrari A, Kramer M, Parodi K, Scholz M and Sommerer F 2010 The FLUKA Monte Carlo code coupled with the local effect model for biological calculations in carbon ion therapy Phys. Med. Biol. 55 4273-89 · DOI
- Morgan W F 2003a Non-targeted and delayed effects of exposure to ionizing radiation: I. Radiation- induced genomic instability and bystander effects in vitro Radiat. Res. 159 567-80 · DOI
- Morgan W F 2003b Non-targeted and delayed effects of exposure to ionizing radiation: II. Radiation- induced genomic instability and bystander effects in vivo, clastogenic factors and transgenerational effects Radiat. Res. 159 581-96 · DOI
- Mothersill C and Seymour C B 1998 Mechanisms and implications of genomic instability and other delayed effects of ionizing radiation exposure Mutagenesis 13 421-6 · DOI
- Nikjoo H, Bolton C E, Watanabe R, Terrissol M, O'Neill P and Goodhead D T 2002 Modelling of DNA damage induced by energetic electrons (100 eV to 100 keV) Radiat. Prot. Dosim. 99 77-80 · DOI
- Watanabe R, Rahmanian S and Nikjoo H 2015 Spectrum of radiation-induced clustered non-DSB damage-a Monte Carlo track structure modeling and calculations Radiat Res 183 525-40 · DOI
- Worku M, Fersht N, Martindale C, Funes J M and Short S C 2013 Sequential transformation of mesenchymal stem cells is associated with increased radiosensitivity and reduced DNA repair capacity Radiat. Res. 179 698-706 · DOI
- Wright E G 2010 Manifestations and mechanisms of non-targeted effects of ionizing radiation Mutat. Res. 687 28-33 · DOI
- Wright E G and Coates P J 2006 Untargeted effects of ionizing radiation: implications for radiation pathology Mutat. Res. 597 119-32 · DOI
- Yajima H, Fujisawa H, Nakajima N I, Hirakawa H, Jeggo P A, Okayasu R and Fujimori A 2013 The complexity of DNA double strand breaks is a critical factor enhancing end-resection DNA Repair (Amst.) 12 936-46 · DOI
- Authors
- Stewart, R. D., Streitmatter, S. W., Argento, D. C., Kirkby, C., Goorley, J. T., Moffitt, G., Jevremovic, T., & Sandison, G. A.
- Affiliations
- University of Washington (US)
- University of Utah (US)
- University of Calgary (CA)
- Los Alamos National Laboratory (US)
- The University of Utah
- Venue
- Physics in Medicine & Biology
- Publisher
- IOP Publishing
- Published
- 2015-10-09
- Volume
- 60
- Issue
- 21
- Pages
- 8249-8274
- ISSN
- 0031-9155 (ISSN-L)
- 1361-6560
- OpenAlex
- W2251384621
- Cited by
- 103
- References
- 85
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 13 · 2023: 3 · 2022: 9 · 2021: 9 · 2020: 14 · 2019: 15 · 2018: 11 · 2017: 12 · 2016: 5 · 2015: 1
- FWCI
- 7.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Physics in Medicine and Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Energy
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Physical Sciences › Physics and Astronomy › Radiation › Advanced Radiotherapy Techniques
- Keywords
- DNA double-strand breaks, relative biological effectiveness, radiative transfer, fission neutrons, proton pencil beam, Bragg peak, tumor hypoxia, oxygen dependence, X-rays, gamma radiation, particle therapy
- MeSH terms
- Computer Simulation, Gamma Rays, Humans, Monte Carlo Method, Neutrons, Protons, Relative Biological Effectiveness, X-Rays, Photons, DNA Breaks, Double-Stranded
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
