PURPOSE: Simulation of indirect damage originating from the attack of free radical species produced by ionizing radiation on biological molecules based on the independent pair approximation is investigated in this work. In addition, a new approach, relying on the independent pair approximation that is at the origin of the independent reaction time (IRT) method, is proposed in the chemical stage of Geant4-DNA. METHODS: This new approach has been designed to respect the current Geant4-DNA chemistry framework while proposing a variant IRT method. Based on the synchronous algorithm, this implementation allows us to access the information concerning the position of radicals and may make it more convenient for biological damage simulations. Estimates of the evolution of free species as well as biological hits in a segment of DNA chromatin fiber in Geant4-DNA were compared for the dynamic time step approach of the step-by-step (SBS) method, currently used in Geant4-DNA, and this newly implemented IRT. RESULTS: Results show a gain in computation time of a factor of 30 for high LET particle tracks with a better than 10% agreement on the number of DNA hits between the value obtained with the IRT method as implemented in this work and the SBS method currently available in Geant4-DNA. CONCLUSION: Offering in Geant4-DNA more efficient methods for the chemical step based on the IRT method is a task in progress. For the calculation of biological damage, information on the position of chemical species is a crucial point. This can be achieved using the method presented in this paper.

Department of Radiation Convergence Engineering Yonsei University Wonju 26493 Korea

Department of Radiation Dosimetry Nuclear Physics Institute of the CAS Prague Czech Republic

Department of Radiation Oncology University of California San Francisco San Francisco CA 94115 USA

IRSN Institut de Radioprotection et de Sûreté Nucléaire BP17 Fontenay aux Roses 92262 France

KEK 1 1 Oho Tsukuba Ibaraki 305 0801 Japan

Radiation Laboratory University of Notre Dame Notre Dame In 46556 USA

Université de Bordeaux CNRS IN2P3 UMR5797 Centre d'Études Nucléaires de Bordeaux Gradignan Gradignan 33175 France

See more in PubMed

Mavragani IV, Nikitaki Z, Kalospyros SA, Georgakilas AG. Ionizing radiation and complex DNA damage: from prediction to detection challenges and biological significance. Cancers. 2019;11:1789. PubMed PMC

Meylan S, Incerti S, Karamitros M, et al. Simulation of early DNA damage after the irradiation of a fibroblast cell nucleus using Geant4‐DNA. Sci Rep. 2017;7:11923. PubMed PMC

Lampe N, Karamitros M, Breton V, et al. Mechanistic DNA damage simulations in Geant4‐DNA part 1: a parameter study in a simplified geometry. Phys Med. 2018;48:135–145. PubMed

Lampe N, Karamitros M, Breton V, et al. Mechanistic DNA damage simulations in Geant4‐DNA part 2: electron and proton damage in a bacterial cell. Phys Med. 2018;48:146–155. PubMed

Sakata D, Lampe N, Karamitos M, et al. Evaluation of radiation DNA damage in a fractal cell nucleus model using Geant4‐DNA. Phys Med. 2019;62:152–157. PubMed

Meylan S, Vimont U, Incerti S, Clairand I, Villagrasa C. Geant4‐DNA simulations using complex DNA geometries generated by the DnaFabric tool. Comput Phys Commun. 2016;204:159–169.

Buxton GV, Greeanstock CL, Helman WP, Ross AB. Critical review of rate constants for reactions of hydrated electrons, hydrogen atoms and hydroxyl radicals (·OH/·O‐) − in aqueous solution. J Phys Chem Ref Data. 1988;17:513–886.

Bluett VM, Green NJB. Competitive diffusion‐influenced reaction of a reactive particle with two static sinks. J Phys Chem A. 2006;110:4738–4752. PubMed

Agmon N. Diffusion with back reaction. J Chem Phys. 1984;8:2811.

Clifford P, Green NJB, Oldfield MJ, Pilling MJ, Pimblot SM. Stochastic models of multi‐species kinetics in radiation‐induced spurs. J Chem Soc Faraday Trans. 1986;82:2673–2689.

Karamitros M, Luan S, Bernal MA, et al. Diffusion‐controlled reactions modeling in Geant4‐DNA. J Comput Phys. 2014;274:841–882.

Uehara S, Nikjoo H. Monte Carlo simulation of water radiolysis for low‐energy charged particles. J Radiat Res. 2006;47:69–81. PubMed

Green NJB, Pilling MJ, Pimblott SM, Clifford P. Stochastic modeling of fast kinetics in a radiation track. J Phys Chem. 1990;94:251–258.

Frongillo Y, Goulet T, Fraser M‐J, Cobut V, Patau JP, Jay‐Gerin J‐P. Monte Carlo simulation of fast electron and proton tracks in liquid water—II. Nonhomogen Chem Radiat Phys Chem. 1998;51:245–254.

Clifford P, Green NJB, Pilling MJ. Monte Carlo Simulation of diffusion and reaction in radiation‐induced spurs. Comparison with analytic models. J Phys Chem. 1982;86:1322–1327.

Agostinelli S, Allison J, Amako K, et al. Geant4—a simulation toolkit. Nucl Instrum Methods Phys Res A. 2003;506:250–303.

Allison J, Amako K, Apostolakis J, et al. Geant4 developments and applications. IEEE Trans Nucl Sci. 2006;53:270.

Allison J, Amako K, Apostolakis J, et al. Recent developments in GEANT4. Nucl Instrum Methods Phys Res A. 2016;835:186–225.

Incerti S, Baldacchino G, Bernal M, et al. The Geant4‐DNA project. Int J Model Simul Sci Comput. 2010;1:157–178.

Incerti S, Ivanchenko A, Karamitros M, et al. Comparison of Geant4 very low energy cross section models with experimental data in water. Med Phys. 2010;37:4692–4708. PubMed

Bernal MA, Bordage MC, Brown J, et al. Track structure modeling in liquid water: a review of the Geant4‐DNA very low energy extension of the Geant4 Monte Carlo simulation toolkit. Phys Med. 2015;31:861–874. PubMed

Incerti S, Kyriakou I, Bernal MA, et al. Geant4‐DNA example applications for track structure simulations in liquid water: a report from the Geant4‐DNA Project. Med Phys. 2018;45:722–739. PubMed

Schuemann J, McNamara AL, Ramos‐Méndez J, et al. TOPAS‐nBio: an extension to the TOPAS simulation toolkit for cellular and sub‐cellular radiobiology. Radiat Res. 2018;191:125–138. PubMed PMC

Perl J, Shin J, Schümann J, Faddegon B, Paganetti H. TOPAS: an innovative proton Monte Carlo platform for research and clinical applications. Med Phys. 2012;39:6818–6837. PubMed PMC

Ramos‐ Méndez J, Shin WG, Karamitros M, et al. Independent reaction times method in Geant4‐DNA: implementation and performance. Med Phys. 2020;47:5919–5930. PubMed PMC

Karamitros M, Brown J, Lampe N, et al. Implementing the Independent Reaction Time method in Geant4 for radiation chemistry simulations. arXiv:2006.14225.

Udovičić LJ, Mark F, Bothe E, Udovicic LJ. Yields of single‐strand breaks in double‐stranded calf thymus DNA irradiated in aqueous solution in the presence of oxygen and scavengers. Radiat Res. 2006;140:166. PubMed

Kreipl MS, Fridland W, Paretzke HG. Time‐ and space‐resolved Monte Carlo study of water radiolysis for photon, electron and ion irradiation. Radiat Environ Biophys. 2009;48:11–20. PubMed

Goulet T, Jay‐Gerin J‐P. On the reactions of hydrated electrons with OH⋅ and H3O+. Analysis of photoionization experiments. J Chem Phys. 1992;96:5076.

Plante I, Devroye L. Considerations for the independent reaction times and step‐by‐step methods for radiation chemistry simulations. Radiat Phys Chem. 2017;139:157–172.

Shin W‐G, Ramos‐Mendez J, Faddegon B, et al. Evaluation of the influence of physical and chemical parameters on water radiolysis simulations under MeV electron irradiation using Geant4‐DNA. J Appl Phys. 2019;126:104301.

Delage E, Pham QT, Karamitros M, et al. PDB4DNA: implementation of DNA geometry from Protein Data Bank (PDB) description for Geant4‐DNA Monte‐Carlo simulations. Comput Phys Commun. 2015;192:282–288.

Tang N, Bueno M, Meylan S, et al. Influence of chromatin compaction on simulated early radiation‐induced DNA damage using Geant4‐DNA. Med. Phys. 2019;46:1501–1511. PubMed

Kinner A, Wu W, Staudt C, Iliakis G. γ‐H2AX in recognition and signaling of DNA double‐strand breaks in the context of chromatin. Nucleic Acids Res. 2008;36:5678–5694. PubMed PMC

Tang N, Bueno M, Meylan S, et al. Assessment of radio‐induced damage in endothelial cells irradiated with 40 kVp, 220 kVp, and 4 MV x‐rays by means of micro and nanodosimetric calculations. Int J Mol S. 2019;20:6204. PubMed PMC

LaVverne JA. OH radicals and oxidizing products in the gamma radiolysis of water. Radiat Res. 2000;153:53–196. PubMed

Jay‐Gerin J‐P, Ferradini C. A new estimate of the radical yield at early times in the radiolysis of liquid water. Chem Phys Lett. 2000;317:388–391.

Jonah CD, Miller JR. Yield and Decay Of The Hydroxyl Radical From 200ps to 3ns. J Phys Chem. 1977;81:1974–1976.

Omar AK, El S, Uli J, et al. Time‐dependent radiolytic yield of OH• radical studied by picosecond pulse radiolysis. J Phys Chem A. 2011;115:12212–12216. PubMed

Shiraishi H, Katsumura Y, Hiroishi D, Ishigure K, Washio M. Pulse‐radiolysis study on the yield of hydrated electron at elevated temperatures. J Phys Chem. 1988;92:3011–3017.

Sumiyoshi T, Katayama M. The yield of hydrated electrons at 30 Picoseconds. Chem Lett. 1982;11:1887–1890.

Hunt JW, Wolff RK, Bronskill MJ, Jonah CD, Hart EJ, Matheson MS. Radiolytic yields of hydrated electrons at 30 to 1000 picoseconds after energy absorption. J Phys Chem. 1973;77:425–426.

Wolff RK, Bronskill MJ, Aldrich JE, Hunt JW. Picosecond pulse radiolysis. IV. Yield of the solvated electron at 30 picoseconds. J Phys Chem. 1973;77:1350–1355.

Buxton GV. Nanosecond Pulse Radiolysis of Aqueous Solutions Containing Proton and Hydroxyl Radical Scavengers. Proceedings of the Royal Society of London A: Mathematical, Physical and Engineering Sciences; 1972: 328. 10.1098/rspa.1972.0065 DOI

Muroya Y, Lin M, Wu G, et al. A re‐evaluation of the initial yield of the hydrated electron in the picosecond time range. Radiat Phys Chem. 2005;72:169–172.

Pikaev AK, Kabakchi SA, Zansokhova AA. Yields and reactions of hydrogen ions on radiolysis of water and aqueous solutions. Faraday Discuss Chem Soc. 1977;63:112–123.

Cercek B, Kongshaug M. Hydrogen ion yields in the radiolysis of neutral aqueous solutions. J Phys Chem. 1969;73:2056–2058. PubMed

Anderson RF, Vojnovic B, Michael BD. The radiation‐chemical yields of H3O+ and OH– as determined by nanosecond conductimetric measurements. Radiat Phys Chem. 1977;1985:301–303.

Schmidt KH, Ander SM. Formation and recombination of the hydronium ion (H3O�) and hydroxide in irradiated water. J Phys Chem. 1969;73:2846–2852.

Elliot AJ, Chenier MP, Ouellette DC, et al. Temperature dependence of G values for H2O and D2O irradiated with low linear energy transfer radiation. J Chem Soc Faraday Trans. 1993;89:1193–1197.

Appleby A, Schwarz HA. Radical and molecular yields in water irradiated by gamma‐rays and heavy ions. J Phys Chem. 1969;73:1937–1941.

Draganic ZD, Draganic IG. Formation of primary reducing yields (Geaq– and GH2) in the radiolysis of aqueous solutions of some positive ions. Int J Radiat Phys Chem. 1975;7:381–386.

LaVerne JA, Pimblott SM. Scavenger and time dependences of radicals and molecular products in the electron radiolysis of water: examination of experiments and models. J Phys Chem. 1991;95:3196–3206.

Draganic ZD, Draganic IG. Formation of primary hydrogen atom yield (GH) in the gamma radiolysis of water. J Phys Chem. 1972;76:2733–2737.

TOPAS-nBio validation for simulating water radiolysis and DNA damage under low-LET irradiation