Simulación de los efectos radiobiológicos en el ADN inducidos por partículas alfa del Ra223 utilizando Geant4-DNA

ilustraciones, tablas

Autores:: Montufar Hidalgo, Diego Luis

Tipo de recurso:

Fecha de publicación:: 2021

Institución:: Universidad Nacional de Colombia

Repositorio:: Universidad Nacional de Colombia

Idioma:: spa

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dc.title.spa.fl_str_mv	Simulación de los efectos radiobiológicos en el ADN inducidos por partículas alfa del Ra223 utilizando Geant4-DNA
dc.title.translated.eng.fl_str_mv	Simulation of radiobiological effects on DNA induced by alpha particles of Ra223 using Geant4-DNA
title	Simulación de los efectos radiobiológicos en el ADN inducidos por partículas alfa del Ra223 utilizando Geant4-DNA
spellingShingle	Simulación de los efectos radiobiológicos en el ADN inducidos por partículas alfa del Ra223 utilizando Geant4-DNA 530 - Física Efectos de la radiación Radiation effects Genética Genetics Radiobiología Radio 223 Partículas alfa Radiación Ionizante ADN Daño directo al ADN Monte Carlo Geant4-DNA Protein Data Bank Radiobiology Radium 223 Alpha Particles Ionizing Radiation DNA Direct DNA Damage Protein Data Bank Monte Carlo Geant4-DNA
title_short	Simulación de los efectos radiobiológicos en el ADN inducidos por partículas alfa del Ra223 utilizando Geant4-DNA
title_full	Simulación de los efectos radiobiológicos en el ADN inducidos por partículas alfa del Ra223 utilizando Geant4-DNA
title_fullStr	Simulación de los efectos radiobiológicos en el ADN inducidos por partículas alfa del Ra223 utilizando Geant4-DNA
title_full_unstemmed	Simulación de los efectos radiobiológicos en el ADN inducidos por partículas alfa del Ra223 utilizando Geant4-DNA
title_sort	Simulación de los efectos radiobiológicos en el ADN inducidos por partículas alfa del Ra223 utilizando Geant4-DNA
dc.creator.fl_str_mv	Montufar Hidalgo, Diego Luis
dc.contributor.advisor.none.fl_str_mv	Bernal Rodriguez, Mario Antonio Plazas, María Cristina
dc.contributor.author.none.fl_str_mv	Montufar Hidalgo, Diego Luis
dc.contributor.datamanager.none.fl_str_mv	Carlos Arturo Clavijo Ramírez
dc.subject.ddc.spa.fl_str_mv	530 - Física
topic	530 - Física Efectos de la radiación Radiation effects Genética Genetics Radiobiología Radio 223 Partículas alfa Radiación Ionizante ADN Daño directo al ADN Monte Carlo Geant4-DNA Protein Data Bank Radiobiology Radium 223 Alpha Particles Ionizing Radiation DNA Direct DNA Damage Protein Data Bank Monte Carlo Geant4-DNA
dc.subject.decs.none.fl_str_mv	Efectos de la radiación Radiation effects Genética Genetics
dc.subject.proposal.spa.fl_str_mv	Radiobiología Radio 223 Partículas alfa Radiación Ionizante ADN Daño directo al ADN Monte Carlo Geant4-DNA
dc.subject.proposal.eng.fl_str_mv	Protein Data Bank Radiobiology Radium 223 Alpha Particles Ionizing Radiation DNA Direct DNA Damage Protein Data Bank Monte Carlo Geant4-DNA
description	ilustraciones, tablas
publishDate	2021
dc.date.accessioned.none.fl_str_mv	2021-07-26T22:17:46Z
dc.date.available.none.fl_str_mv	2021-07-26T22:17:46Z
dc.date.issued.none.fl_str_mv	2021-07-23
dc.type.spa.fl_str_mv	Trabajo de grado - Maestría
dc.type.driver.spa.fl_str_mv	info:eu-repo/semantics/masterThesis
dc.type.version.spa.fl_str_mv	info:eu-repo/semantics/acceptedVersion
dc.type.content.spa.fl_str_mv	Text
dc.type.redcol.spa.fl_str_mv	http://purl.org/redcol/resource_type/TM
status_str	acceptedVersion
dc.identifier.uri.none.fl_str_mv	https://repositorio.unal.edu.co/handle/unal/79848
dc.identifier.instname.spa.fl_str_mv	Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv	Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv	https://repositorio.unal.edu.co/
url	https://repositorio.unal.edu.co/handle/unal/79848 https://repositorio.unal.edu.co/
identifier_str_mv	Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv	spa
language	spa
dc.relation.references.spa.fl_str_mv	[1] P. Brown, “American Martyrs to Science Through the Roentgen Ray,” Radiology, vol. 28, no. 5, pp. 633–633, May 1937. [2] E. J. H. and A. J. Giaccia, Radiobiology for the radiologist, 7th ed. Philadelphia, PA 19103 USA: Springer Science and Business Media LLC, 2012. [3] C. S. Sureka and C. Armpilia, Radiation Biology for Medical Physicists. CRC Press, Taylor & Francis Group, 2017. [4] N. Tang, M. Bueno, S. Meylan, S. Incerti, I. Clairand, and C. Villagrasa, “SIMULATION OF EARLY RADIATION-INDUCED DNA DAMAGE ON DIFFERENT TYPES OF CELL NUCLEI,” Radiat. Prot. Dosimetry, vol. 183, no. 1–2, pp. 26–31, May 2019. [5] S. Meylan et al., “Simulation of early DNA damage after the irradiation of a fibroblast cell nucleus using Geant4-DNA,” Sci. Rep., vol. 7, no. 1, p. 11923, Dec. 2017. [6] N. Lampe et al., “Mechanistic DNA damage simulations in Geant4-DNA Part 2: Electron and proton damage in a bacterial cell,” Phys. Medica, vol. 48, pp. 146–155, Apr. 2018. [7] D. Sakata et al., “Evaluation of early radiation DNA damage in a fractal cell nucleus model using Geant4-DNA,” Phys. Medica, vol. 62, pp. 152–157, Jun. 2019. [8] E. Burgio, P. Piscitelli, and L. Migliore, “Ionizing Radiation and Human Health: Reviewing Models of Exposure and Mechanisms of Cellular Damage. An Epigenetic Perspective,” Int. J. Environ. Res. Public Health, vol. 15, no. 9, p. 1971, Sep. 2018. [9] S. Agostinelli et al., “GEANT4 - A simulation toolkit,” Nucl. Instruments Methods Phys. Res. Sect. A Accel. Spectrometers, Detect. Assoc. Equip., vol. 506, no. 3, pp. 250–303, Jul. 2003. [10] D. T. Goodhead, J. Thacker, and R. Cox, “Effects of Radiations of Different Qualities on Cells: Molecular Mechanisms of Damage and Repair,” Int. J. Radiat. Biol., vol. 63, no. 5, pp. 543–556, Jan. 1993. [11] E. Delage et al., “PDB4DNA: Implementation of DNA geometry from the Protein Data Bank (PDB) description for Geant4-DNA Monte-Carlo simulations,” Comput. Phys. Commun., vol. 192, pp. 282–288, Jul. 2015. [12] H. M. Berman, G. J. Kleywegt, H. Nakamura, and J. L. Markley, “The protein data bank at 40: Reflecting on the past to prepare for the future,” in Structure, 2012, vol. 20, no. 3, pp. 391–396. [13] A. J. Astudillo-Velázquez and L. Paredes-Gutiérrez, “Reflexiones sobre el uso terapéutico de 223 RaCl 2 para metástasis ósea derivada de cáncer de próstata resistente a la castración,” 2015. [14] United Nations Scientific Committee on the Effects Radiation of Atomic Radiation (UNSCEAR), “Sources, Effects and Risks of Ionizing Radiation,” New York, 1988. [15] Sociedad Española de Física Médica, Fundamentos de Física Médica: Volumen 8. Radiobiología y principios de Oncología, ADI Servic. Madrid, 2016. [16] U. H. Ehling, “Quantification of the Genetic Risk of Environmental Mutagens,” Risk Anal., vol. 8, no. 1, pp. 45–57, 1988. [17] K. Sankaranarayanan, “Genetic effects of ionising radiation in man,” Annals of the ICRP, vol. 22, no. 1. No longer published by Elsevier, pp. 75–94, 01-Jan-1991. [18] J. Boice Jr et al., “ICRP Publication 118. ICRP Statement on Tissue Reactions and Early and Late Effects of Radiation in Normal Tissues and Organs - Threshold Doses for Tissue Reactions in a Radiation Protection Context,” 2011. [19] L. de la F. Rosales, “A Monte Carlo Study of the Direct and Indirect DNA Damage Induced by Ionizing Radiation .,” p. 131, 2018. [20] S. Incerti et al., “The Geant4-DNA project,” Int. J. Model. Simulation, Sci. Comput., vol. 1, no. 2, pp. 157–178, 2010. [21] S. Incerti, M. Douglass, S. Penfold, S. Guatelli, and E. Bezak, “Review of Geant4-DNA applications for micro and nanoscale simulations,” Phys. Medica, vol. 32, no. 10, pp. 1187–1200, Oct. 2016. [22] I. Plante and F. A., “Monte-Carlo Simulation of Ionizing Radiation Tracks,” in Applications of Monte Carlo Methods in Biology, Medicine and Other Fields of Science, InTech, 2011. [23] J. C. Forster, M. J. J. Douglass, W. M. Phillips, and E. Bezak, “Monte Carlo Simulation of the Oxygen Effect in DNA Damage Induction by Ionizing Radiation,” Radiat. Res., vol. 190, no. 3, p. 248, Jun. 2018. [24] S. Incerti et al., “Geant4-DNA example applications for track structure simulations in liquid water: A report from the Geant4-DNA Project,” Med. Phys., vol. 45, no. 8, pp. e722–e739, Aug. 2018. [25] G. Sgouros et al., “MIRD pamphlet No. 22 (Abridged): Radiobiology and dosimetry of α-particle emitters for targeted radionuclide therapy,” Journal of Nuclear Medicine, vol. 51, no. 2. J Nucl Med, pp. 311–328, 01-Feb-2010. [26] C. Villagrasa, Z. Francis, and S. Incerti, “Physical models implemented in the GEANT4-DNA extension of the GEANT-4 toolkit for calculating initial radiation damage at the molecular level.,” Radiat. Prot. Dosimetry, vol. 143, no. 2–4, pp. 214–8, Feb. 2011. [27] S. Meylan, U. Vimont, S. Incerti, I. Clairand, and C. Villagrasa, “Geant4-DNA simulations using complex DNA geometries generated by the DnaFabric tool,” Comput. Phys. Commun., vol. 204, pp. 159–169, Jul. 2016. [28] C. Villagrasa et al., “Geant4-DNA simulation of DNA damage caused by direct and indirect radiation effects and comparison with biological data.,” EPJ Web Conf., vol. 153, p. 04019, 2017. [29] M. B. Tavakoli, H. Moradi, H. Khanahmad, and M. Hosseini, “Circular Mitochondrial DNA: A Geant4-DNA User Application for Evaluating Radiation-induced Damage in Circular Mitochondrial DNA.,” J. Med. Signals Sens., vol. 7, no. 4, pp. 213–219, 2017. [30] K. P. Chatzipapas et al., “Quantification of <scp>DNA</scp> double‐strand breaks using Geant4‐ <scp>DNA</scp>,” Med. Phys., vol. 46, no. 1, p. mp.13290, Dec. 2018. [31] P. Shamshiri, G. Forozani, and A. Zabihi, “An investigation of the physics mechanism based on DNA damage produced by protons and alpha particles in a realistic DNA model,” Nucl. Instruments Methods Phys. Res. Sect. B Beam Interact. with Mater. Atoms, vol. 454, pp. 40–44, Sep. 2019. [32] Y. Alexandra and P. Giron, “Aproximación computacional vía geant4 a la esterilización de membranas amnióticas humanas usando radiación ionizante,” 2017. [33] A. Marcela and F. Torres, “Estimation of the relative biological effectiveness of heavy ions using the dose-mean transfer energy,” 2019. [34] “PDB-101: Molecule of the Month: DNA.” [Online]. Available: http://pdb101.rcsb.org/motm/23. [Accessed: 26-Nov-2020]. [35] A. H.-J. Wang et al., “Molecular structure of a left-handed double helical DNA fragment at atomic resolution,” Nature, vol. 282, no. 5740, pp. 680–686, Dec. 1979. [36] R. E. Dickerson, “The DNA Helix and How it is Read,” Sci. Am., vol. 249, no. 6, pp. 94–111, Dec. 1983. [37] T. Schalch, S. Duda, D. F. Sargent, and T. J. Richmond, “X-ray structure of a tetranucleosome and its implications for the chromatin fibre,” Nature, vol. 436, no. 7047, pp. 138–141, Jul. 2005. [38] M. Pertea and S. L. Salzberg, “Between a chicken and a grape: estimating the number of human genes,” Genome Biol., vol. 11, no. 5, p. 206, May 2010. [39] H. R. Drew et al., “Structure of a B-DNA dodecamer: conformation and dynamics.,” Proc. Natl. Acad. Sci., vol. 78, no. 4, pp. 2179–2183, Apr. 1981. [40] B. N. Conner, C. Yoon, J. L. Dickerson, and R. E. Dickerson, “Helix geometry and hydration in an A-DNA tetramer: IC-C-G-G,” J. Mol. Biol., vol. 174, no. 4, pp. 663–695, Apr. 1984. [41] F. M. Khan, L. Wilkins, and Williams, The Physics of Radiation Therapy, 4th ed., vol. 37, no. 3. Baltimore and Philadelphia: Wiley-Blackwell, 2010. [42] D. T. B. Pedro Andreo and and F. H. A. Alan E. Nahum, Jan Seuntjens, Fundamentals of Ionizing Radiation Dosimetry, vol. 2. Wiley, 2017. [43] E. B. Podgorsak, Radiation Physics for Medical Physicists. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. [44] M. J. Berger et al., Stopping powers and ranges for protons and alpha particles. ICRU report 49, vol. os25, no. 2. SAGE Publications, 1993. [45] M. J. Berger et al., Stopping Powers for Electrons and Positrons. ICRU Report 37, vol. os19, no. 2. 1984. [46] A. Allisy, W. A. Jennings, A. M. Kellerer, J. W. Müller, H. H. Rossi, and S. M. Seltzer, “International Commission on Radiation Units and Measurements. Report 60,” J. Int. Comm. Radiat. Units Meas., vol. os31, no. 1, p. NP-NP, Dec. 1998. [47] L. T. Dauer et al., “Radiation safety considerations for the use of 223RaCl2 de in men with castration-resistant prostate cancer,” Health Phys., vol. 106, no. 4, pp. 494–504, Apr. 2014. [48] Z. Ahmadi Ganjeh, M. Eslami-Kalantari, M. Ebrahimi Loushab, and A. A. Mowlavi, “Simulation of direct DNA damages caused by alpha particles versus protons,” Nucl. Instruments Methods Phys. Res. Sect. B Beam Interact. with Mater. Atoms, vol. 473, pp. 10–15, Jun. 2020. [49] E. Herranz Muelas, “Simulaciones Monte Carlo para radioterapia intraoperatoria con haces de electrones,” Universidad Complutense de Madrid, 2013. [50] P. B. Ibáñez Cuenca, “Implementation and validation of ultra-fast dosimetric tools for IORT,” Universidad Complutense de Madrid, 2018. [51] R. Shukla, N. P. Patel, H. P. Yadav, and V. Kaushal, “A Monte Carlo simulation study on the effectiveness of electron filters designed for telecobalt radiation therapy treatment,” Int. J. Radiat. Res., vol. 17, No. 2, p. 12, 2019. [52] F. J. García Cases, “Protección radiológica en radioterapia intraoperatoria mediante un acelerador portátil de electrones,” Universidad Católica de Murcia, 2016. [53] S. INCERTI et al., “THE GEANT4-DNA PROJECT,” Int. J. Model. Simulation, Sci. Comput., vol. 01, no. 02, pp. 157–178, Jun. 2010. [54] S. Incerti et al., “Geant4-DNA example applications for track structure simulations in liquid water: A report from the Geant4-DNA Project,” Med. Phys., vol. 45, no. 8, pp. e722–e739, Aug. 2018. [55] “Physics List.” [Online]. Available: http://geant4-dna.in2p3.fr/styled-3/styled-9/index.html. [Accessed: 04-Mar-2021]. [56] “Geant4 General Particle Source — Book For Application Developers 10.7 documentation.” [Online]. Available: https://geant4-userdoc.web.cern.ch/UsersGuides/ForApplicationDeveloper/html/GettingStarted/generalParticleSource.html#g4gps. [Accessed: 04-Mar-2021]. [57] E. Choi, K. S. Chon, and M. G. Yoon, “Evaluating direct and indirect effects of low-energy electrons using Geant4-DNA,” Radiat. Eff. Defects Solids, vol. 175, no. 11–12, pp. 1042–1051, Nov. 2020. [58] “Plot Digitizer.” [Online]. Available: http://plotdigitizer.sourceforge.net/. [Accessed: 03-Apr-2021]. [59] A. Ottolenghi, M. Merzagora, and H. G. Paretzke, “DNA complex lesions induced by protons and α-particles: Track structure characteristics determining linear energy transfer and particle type dependence,” Radiat. Environ. Biophys., vol. 36, no. 2, pp. 97–103, Jun. 1997. [60] M. A. Bernal, C. E. deAlmeida, C. Sampaio, S. Incerti, C. Champion, and P. Nieminen, “The invariance of the total direct DNA strand break yield,” Med. Phys., vol. 38, no. 7, pp. 4147–4153, Jun. 2011. [61] P. Pater et al., “Proton and light ion RBE for the induction of direct DNA double strand breaks,” Med. Phys., vol. 43, no. 5, pp. 2131–2140, Apr. 2016. [62] S. Incerti et al., “Energy deposition in small-scale targets of liquid water using the very low energy electromagnetic physics processes of the Geant4 toolkit,” Nucl. Instruments Methods Phys. Res. Sect. B Beam Interact. with Mater. Atoms, vol. 306, pp. 158–164, Jul. 2013. [63] “IAEA. Relative biological effectiveness in ion beam therapy.” [64] A. Zabihi et al., “Computational approach to determine the relative biological effectiveness of fast neutrons using the Geant4-DNA toolkit and a DNA atomic model from the Protein Data Bank,” Phys. Rev. E, vol. 99, no. 5, p. 052404, May 2019.
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dc.rights.license.spa.fl_str_mv	Atribución-NoComercial-SinDerivadas 4.0 Internacional
dc.rights.uri.spa.fl_str_mv	http://creativecommons.org/licenses/by-nc-nd/4.0/
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rights_invalid_str_mv	Atribución-NoComercial-SinDerivadas 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ http://purl.org/coar/access_right/c_abf2
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dc.format.extent.spa.fl_str_mv	135 páginas
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dc.publisher.spa.fl_str_mv	Universidad Nacional de Colombia
dc.publisher.program.spa.fl_str_mv	Bogotá - Ciencias - Maestría en Física Médica
dc.publisher.department.spa.fl_str_mv	Departamento de Física
dc.publisher.faculty.spa.fl_str_mv	Facultad de Ciencias
dc.publisher.place.spa.fl_str_mv	Bogotá, Colombia
dc.publisher.branch.spa.fl_str_mv	Universidad Nacional de Colombia - Sede Bogotá
institution	Universidad Nacional de Colombia
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spelling	Atribución-NoComercial-SinDerivadas 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Bernal Rodriguez, Mario Antonio9a4f4c6da6dbba812be3153fe9d7e22cPlazas, María Cristina3a0ca95e85d6f86f5d25028ada0b1516Montufar Hidalgo, Diego Luisf6363622be565410aef352f6e8b97df3Carlos Arturo Clavijo Ramírez2021-07-26T22:17:46Z2021-07-26T22:17:46Z2021-07-23https://repositorio.unal.edu.co/handle/unal/79848Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, tablasEl efecto directo de las partículas alfa generadas del decaimiento radiactivo del Radio 223 hacia una molécula de ADN-B (1ZBB) del Protein Data Bank (PDB) como punto final biológico, se investigó utilizando las extensiones de Geant4-DNA simulando el transporte de partículas alfa primarias con energías de 3 a 20 MeV y sus partículas secundarias en agua líquida para estudiar el daño radiobiológico en forma de SSB y DSB. Las simulaciones se realizaron en un medio de agua esférico el cual contiene la molécula de ADN, en el que se emitieron partículas alfa de forma isotrópica que irradien uniformemente el volumen de agua. Se asumió que las deposiciones de energía de más de 8,22 eV conducen a rupturas de la cadena de ADN. Además, se calcularon los rendimientos directos de SSB y DSB para partículas alfa con diferentes energías incidentes en términos del LET. Los resultados presentaron un acuerdo razonable en términos de tendencia y valor entre los resultados de rendimiento de DSB de este trabajo, otras simulaciones y los datos experimentales disponibles. Se evaluó la efectividad biológica relativa (RBE) para la inducción de rupturas directas de doble cadena de ADN (RBE_DSB) en el ADN que producen los radionúclidos utilizados en terapias dirigidas como emisores de partículas alfa.The direct effect of the alpha particles generated from the radioactive decay of Radium 223 towards a DNA-B molecule (1ZBB) of the Protein Data Bank (PDB) as a biological end point, was investigated using Geant4-DNA extensions simulating the transport of alpha primary particles with energies from 3 to 20 MeV and their secondary particles in liquid water to study radiobiological damage in form of SSB and DSB. The simulations were carried out in a spherical water medium which contains the DNA molecule, in which alpha particles were emitted in an isotropic way that irradiate uniformly the volume of water. Energy deposition of more than 8.22 eV was assumed to lead to DNA strand breaks. Furthermore, direct SSB and DSB yields were calculated for alpha particles with different incident energies in terms of the LET. The results presented a reasonable agreement in terms of trend and value between the DSB performance results of this work, other simulations and the available experimental data. The relative biological effectiveness (RBE) was evaluated for the induction of direct DNA double strand breaks (RBE_DSB) in the DNA that radionuclides used in targeted therapies as emitters of alpha particles produce.MaestríaMagíster en Física MédicaRadiobiología135 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Física MédicaDepartamento de FísicaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá530 - FísicaEfectos de la radiaciónRadiation effectsGenéticaGeneticsRadiobiologíaRadio 223Partículas alfaRadiación IonizanteADNDaño directo al ADNMonte CarloGeant4-DNAProtein Data BankRadiobiologyRadium 223Alpha ParticlesIonizing RadiationDNADirect DNA DamageProtein Data BankMonte CarloGeant4-DNASimulación de los efectos radiobiológicos en el ADN inducidos por partículas alfa del Ra223 utilizando Geant4-DNASimulation of radiobiological effects on DNA induced by alpha particles of Ra223 using Geant4-DNATrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TM[1] P. Brown, “American Martyrs to Science Through the Roentgen Ray,” Radiology, vol. 28, no. 5, pp. 633–633, May 1937.[2] E. J. H. and A. J. Giaccia, Radiobiology for the radiologist, 7th ed. Philadelphia, PA 19103 USA: Springer Science and Business Media LLC, 2012.[3] C. S. Sureka and C. Armpilia, Radiation Biology for Medical Physicists. CRC Press, Taylor & Francis Group, 2017.[4] N. Tang, M. Bueno, S. Meylan, S. Incerti, I. Clairand, and C. Villagrasa, “SIMULATION OF EARLY RADIATION-INDUCED DNA DAMAGE ON DIFFERENT TYPES OF CELL NUCLEI,” Radiat. Prot. Dosimetry, vol. 183, no. 1–2, pp. 26–31, May 2019.[5] S. Meylan et al., “Simulation of early DNA damage after the irradiation of a fibroblast cell nucleus using Geant4-DNA,” Sci. Rep., vol. 7, no. 1, p. 11923, Dec. 2017.[6] N. Lampe et al., “Mechanistic DNA damage simulations in Geant4-DNA Part 2: Electron and proton damage in a bacterial cell,” Phys. Medica, vol. 48, pp. 146–155, Apr. 2018.[7] D. Sakata et al., “Evaluation of early radiation DNA damage in a fractal cell nucleus model using Geant4-DNA,” Phys. Medica, vol. 62, pp. 152–157, Jun. 2019.[8] E. Burgio, P. Piscitelli, and L. Migliore, “Ionizing Radiation and Human Health: Reviewing Models of Exposure and Mechanisms of Cellular Damage. An Epigenetic Perspective,” Int. J. Environ. Res. Public Health, vol. 15, no. 9, p. 1971, Sep. 2018.[9] S. Agostinelli et al., “GEANT4 - A simulation toolkit,” Nucl. Instruments Methods Phys. Res. Sect. A Accel. Spectrometers, Detect. Assoc. Equip., vol. 506, no. 3, pp. 250–303, Jul. 2003.[10] D. T. Goodhead, J. Thacker, and R. Cox, “Effects of Radiations of Different Qualities on Cells: Molecular Mechanisms of Damage and Repair,” Int. J. Radiat. Biol., vol. 63, no. 5, pp. 543–556, Jan. 1993.[11] E. Delage et al., “PDB4DNA: Implementation of DNA geometry from the Protein Data Bank (PDB) description for Geant4-DNA Monte-Carlo simulations,” Comput. Phys. Commun., vol. 192, pp. 282–288, Jul. 2015.[12] H. M. Berman, G. J. Kleywegt, H. Nakamura, and J. L. Markley, “The protein data bank at 40: Reflecting on the past to prepare for the future,” in Structure, 2012, vol. 20, no. 3, pp. 391–396.[13] A. J. Astudillo-Velázquez and L. Paredes-Gutiérrez, “Reflexiones sobre el uso terapéutico de 223 RaCl 2 para metástasis ósea derivada de cáncer de próstata resistente a la castración,” 2015.[14] United Nations Scientific Committee on the Effects Radiation of Atomic Radiation (UNSCEAR), “Sources, Effects and Risks of Ionizing Radiation,” New York, 1988.[15] Sociedad Española de Física Médica, Fundamentos de Física Médica: Volumen 8. Radiobiología y principios de Oncología, ADI Servic. Madrid, 2016.[16] U. H. Ehling, “Quantification of the Genetic Risk of Environmental Mutagens,” Risk Anal., vol. 8, no. 1, pp. 45–57, 1988.[17] K. Sankaranarayanan, “Genetic effects of ionising radiation in man,” Annals of the ICRP, vol. 22, no. 1. 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