In this work, we simulated the passage of charged particle tracks through various regions of the hippocampus of rats, which included the main cell types of various morphology. For each model of the neuron we modeled a cellular body (soma) with nuclear DNA, axon and dendrites, with spines and synaptic receptors distributed on them. With the use of the Geant4 Monte-Carlo method we simulated the physicochemical processes in the hippocampal neurons and the neural networks formed by them under irradiation with charged particles in a wide range of linear energy transfer (LET). The calculation of the formation of molecular damage of various types in the sensitive structures of nerve cells taking into account the processes of water radiolysis after radiation exposure was also carried out. It is predicted that the yield of cluster single-stranded DNA breaks, including base damage, has maximum at LET values in the range of 20-50 keV/μm. The maximum yield of double-stranded DNA breaks per unit of absorbed dose is observed at LET values within 100-200 keV/μm, and the largest yield of cluster double-stranded DNA breaks, including base damage, occurs in the area of LET around 300 keV/μm. The results obtained are in agreement with the published experimental data.
neurons, charged particle track, clustered DNA damage, RBE
1. Greene-Schloesser D., Robbins M.E., Peiffer A.M., Shaw E.G., Wheeler K.T., Chan M.D. Radiation-induced brain injury: a review. Frontiers in oncology, 2012, vol. 2, pp. 1-18. DOI:https://doi.org/10.3389/fonc.2012.00073.
2. Grigor'ev A.I., Krasavin E.A., Ostrovskiy M.A. K ocenke riska biologicheskogo deystviya galakticheskih tyazhelyh ionov v usloviyah mezhplanetnogo poleta. Rossiyskiy fiziologicheskiy zhurnal im. I.M. Sechenova, 2013, t. 99, № 3, s. 273-280. [Grigoriev A.I., Krasavin E.A., Ostrovskiy M.A. To an assessment of risk of galactic heavy ions biological effect in interplanetary flight. Rossiyskiy fiziologicheskiy zhurnal, 2013, vol. 99, no. 3, pp. 273-280. (In Russ.)]
3. Cucinotta F.A., Alp M., Sulzman F.M. et al. Space radiation risks to the central nervous system. Life Sci Sp Res., 2014, vol. 2, pp. 54-69. DOI:https://doi.org/10.1016/j.lssr.2014.06.003.
4. Nelson G.A. Space Radiation and Human Exposures. A Primer. Radiat Res., 2016, vol. 185, no. 4, pp. 349-58. DOI:https://doi.org/10.1667/RR14311.1.
5. Parihar V.K., Allen B.D., Caressi C. Cosmic radiation exposure and persistent cognitive dysfunction. Sci Rep., 2016, vol. 6, p. 34774. DOI:https://doi.org/10.1038/srep34774.
6. Vlkolinsky R., Titova E., Krucker T. et al. Exposure to 56Fe-particle radiation accelerates electrophysiological alterations in the hippocampus of APP23 transgenic mice. Radiat Res., 2010, vol. 173, pp. 342-352. DOI:https://doi.org/10.1667/RR1825.1.
7. Rudobeck E., Nelson G.A., Sokolova I.V., et al. 28Silicon radiation impairs neuronal output in CA1 neurons of mouse ventral hippocampus without altering dendritic excitability. Radiat Res., 2014, vol. 181, no. 4, pp. 407-415. DOI:https://doi.org/10.1667/RR13484.1.
8. Zhang L., Chen L., Sun R. et al. Effects of expression level of DNA repair-related genes involved in the NHEJ pathway on radiation-induced cognitive impairment. J. Radiat. Res., 2013, vol. 54, no. 2, pp. 235-242. DOI:https://doi.org/10.1093/jrr/rrs095.
9. Boreyko A.V., Bugay A.N., Bulanova T.S., Dushanov E.B., Jezkova L., Kulikova E.A., Smirnova E.V., Zadneprianetc M.G., Krasavin E.A. Clustered DNA double-strand breaks and neuroradiobiological effects of accelerated charged particles. Phys. Part. Nucl. Lett., 2018, vol. 15, p. 551.
10. Batova A.S., Bugay A.N., Dushanov E.B. Effect of mutant NMDA receptors on the oscillations in a model of hippocampus. Journal of Bioinformatics and Computational Biology, 2019, vol. 17, no. 1, p. 1940003
11. Batmunkh M., Belov O.V., Bayarchimeg L. et al. Estimation of the spatial energy deposition in CA1 pyramidal neurons under exposure to 12C and 56Fe ion beams. J. Radiat. Res. Appl. Sci., 2015, vol. 8, pp. 498-507. DOI:https://doi.org/10.1016/j.jrras.2015.05.008.
12. Bayarchimeg L., Batmunkh M., Belov O.V. Reconstruction of the neural cell morphology for microdosimetric calculations. ICTP HRCS ppt, 2013, vol. 1, pp. 21-22. Retrieved from http://handsonresearch.org/
13. Alp M., Parihar V.K., Limoli C.L., et al. Irradiation of Neurons with High-Energy Charged Particles: An In Silico Modeling Approach. PLoS Comput Biol., 2015, vol. 11, no. 8, p. e1004428. DOI:https://doi.org/10.1371/journal.pcbi.1004428.
14. Nakajima N.I., Brunton H., Watanabe R. et al. Visualisation of γH2AX Foci Caused by Heavy Ion Particle Traversal; Distinction between Core Track versus Non-Track Damage. PLoS ONE, 2013, vol. 8, no. 8, p. e70107. DOI:https://doi.org/10.1371/journal.pone.0070107.
15. Friedland W., Schmitt E., Kundrat P. et al. Comprehensive track-structure based evaluation of DNA damage by light ions from radiotherapy-relevant energies down to stopping. Sci Rep., 2017, vol. 7, p. 45161.
16. Saha J., Wilson P., Thieberger P. et al. Biological Characterization of Low-Energy Ions with High-Energy Deposition on Human Cells. Radiat Res., 2014, vol. 182, no. 3, pp. 282-291. DOI:https://doi.org/10.1667/rr13747.1.
17. 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, vol. 7, p. 11923.
18. Lampe N., Karamitros M., Breton V. et al. Mechanistic DNA damage simulations in Geant4-DNA part 2: Electron and protondamage in a bacterial cell. Phys Med., 2018, vol. 48, pp. 146-155.
19. Watanabe R., Rahmanian S., Nikjoo H. Spectrum of Radiation-Induced Clustered Non-DSB Damage - A Monte Carlo Track Structure Modeling and Calculations. Radiat Res., 2015, vol. 183, no. 5, pp. 525-540. DOI:https://doi.org/10.1667/rr13902.1.
20. Adam Gh., Bashashin M., Belyakov D. et al. IT ecosystem of the HybriLIT heterogeneous platform for high performance computing and training of IT specialists. Selected Papers of the 8th International Conference «Distributed Computing and Grid-technologies in Science and Education» (GRID 2018), 2018, CEUR-WS.org/Vol.2267
21. Bayarchimeg L., Batmunkh M., Belov O.V., Lkhagva O., Simulation of radiation damage to neural cells with Geant4-DNA. EPJ Web Conf., 2018, vol. 173, no. 2, p. 05005. DOI:https://doi.org/10.1051/epjconf/201817305005.
22. Batmunkh M., Aksenova S.V., Bayarchimeg L., Bugay A.N., Lkhagva O. Optimized Neuron Models for Estimation of Charged Particle Energy Deposition in Hippocampus. Phys. Med., 2019, vol. 57, pp. 88-94, DOI:https://doi.org/10.1016/j.ejmp.2019.01.002
23. Gibbs R.A. et al. [Rat Genome Sequencing Project Consortium] Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature, 2004, vol. 428, pp. 493-521.
24. Nikjoo H., O Neill P., Goodhead D., Terrissol M. Computational modelling of low-energy electron-induced DNA damage by early physical and chemical events. Int. J. Radiat. Biol., 1997, vol. 71, p. 467.
25. Buxton G.V., Greenstock C.L., Helman W.P., Ross A.B. Critical review of rateconstants for reactions of hydrated electrons, hydrogen atoms and hydroxyl radicals (OH/O) in Aqueous Solution. J. Phys. Chem. Ref. Data, 1988, vol. 17, p. 513.
26. Bayarchimeg L., Bugay A., Batmunkh M., Lkhagva O. Evaluation of radiation-inducedeffects in membrane ion channels and receptors. Phys. Part. Nucl. Lett., 2019, vol. 16, pp. 54-62. DOI:https://doi.org/10.1134/S1547477119010059.
27. Batmunkh M., Bugay A.N., Bayarchimeg L., Aksenova S.V., Lkhagva O. Computer Modeling of Radiation - Induced Damage to Hippocampal Cells. Mong. J. Phys., 2019, vol. 5, pp. 76-82.
28. Batmunkh M., Bayarchimeg L., Bugay A.N., Lkhagva O. Monte Carlo track structure simulation in studies of biological effects induced by accelerated charged particles in the central nervous system. EPJ WoC, 2019, vol. 204, p. 04008. DOI:https://doi.org/10.1051/epjconf/201920404008.
29. Hirayama R., Ito A., Tomita M. et al. Contributions of Direct and Indirect Actions in Cell Killing by High-LET Radiations. Radiat Res., 2009, vol. 171, no. 2, pp. 212-218. DOI:https://doi.org/10.1667/rr1490.1.
30. Roots R., Holley W., Chatterjee A. et al. The Formation of Strand Breaks in DNA after High-LET Irradiation: A Comparison of Data from in Vitro and Cellular Systems. International Journal of Radiation Biology, 1990, vol. 58, no. 1, pp. 55-69. DOI:https://doi.org/10.1080/09553009014551431.
31. Alloni D., Campa A., Friedland W. et al. 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/μm LET. Radiat Res., 2013, vol. 179, no. 6, pp. 690-697. DOI:https://doi.org/10.1667/r3043.1.
32. Hoglund E., Stenerlow B. Induction and rejoining of DNA double-strand breaks in normal human skin fibroblasts after exposure to radiation of different linear energy transfer: possible roles of track structure and chromatin organization. Radiat Res., 2001, vol. 155, pp. 818-25.
33. Kozhina R.A., Chausov V.N., Kuzmina E.A., Boreyko A.V. Induction and repair of DNA double-strand breaks in hippocampal neurons of mise of different age after exposure to 60Co -rays in vivo and in vitro. EPJ Web Conf., 2018, vol. 177, p. 06001.
34. Bulanova T.S. Boreyko A.V., Zadneprianetc M.G. et al. Formation of DNA Double-Strand Breaks in Rat Brain Neurons after Irradiation with Krypton Ions (78Kr). Phys. Part. Nuclei Lett., 2019, vol. 16, p. 402. DOI:https://doi.org/10.1134/S1547477119040083.
35. Löbrich M., Cooper P.K., Rydberg B. Non-random distribution of DNA double-strand breaks induced by particle irradiation. Int. J. Radiat. Biol., 1996, vol. 70, no. 5, pp. 493-503.
36. Frankenberg D., Brede H.J., Schrewe U.J. et al. Induction of DNA Double-Strand Breaks by 1H and 4He Ions in Primary Human Skin Fibroblasts in the LET Range of 8 to 124 keV/μm. Radiat Res., 1999, vol. 151, no. 5, pp. 540-549.
37. Campa A., Alloni D., Antonelli F. et al. DNA fragmentation induced in human fibroblasts by 56Fe ions: experimental data and Monte Carlo simulations. Radiat Res., 2009, vol. 171, no. 4, pp. 438-445. DOI:https://doi.org/10.1667/RR1442.1.
