Diverse isotopes such as 2H, 3He, 10Be, 11C and 14C occur in nuclear reactions in ion beam radiotherapy, in cosmic ray shielding, or are intentionally accelerated in dating techniques. However, only a few studies have specifically addressed the biological effects of diverse isotopes and were limited to energies of several MeV/u. A database of simulations with the PARTRAC biophysical tool is presented for H, He, Li, Be, B and C isotopes at energies from 0.5 GeV/u down to stopping. The doses deposited to a cell nucleus and also the yields per unit dose of single- and double-strand breaks and their clusters induced in cellular DNA are predicted to vary among diverse isotopes of the same element at energies < 1 MeV/u, especially for isotopes of H and He. The results may affect the risk estimates for astronauts in deep space missions or the models of biological effectiveness of ion beams and indicate that radiation protection in 14C or 10Be dating techniques may be based on knowledge gathered with 12C or 9Be.

Department of Radiation Dosimetry Nuclear Physics Institute Czech Academy of Sciences Na Truhlářce 39 64 180 00 Prague Czech Republic

Institute of Radiation Medicine Helmholtz Zentrum München GmbH German Research Center for Environmental Health Ingolstädter Landstr 1 85764 Neuherberg Germany

Radiation Biophysics and Radiobiology Group Physics Department University of Pavia 27100 Pavia Italy

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Barendsen G.W. RBE-LET relationships for different types of lethal radiation damage in mammalian cells: Comparison with DNA DSB and an interpretation of differences in radiosensitivity. Int. J. Radiat. Biol. 1994;66:433–436. doi: 10.1080/09553009414551411. PubMed DOI

Prise K.M., Ahnström G., Belli M., Carlsson J., Frankenberg D., Kiefer J., Löbrich M., Michael B.D., Nygren J., Simone G., et al. A review of DSB induction data for varying quality radiations. Int. J. Radiat. Biol. 1998;74:173–184. doi: 10.1080/095530098141564. PubMed DOI

Rydberg B. Radiation-induced DNA damage and chromatin structure. Acta Oncol. 2001;40:682–685. doi: 10.1080/02841860152619070. PubMed DOI

Hada M., Georgakilas A.G. Formation of clustered DNA damage after high-LET irradiation: A review. J. Radiat. Res. 2008;49:203–210. doi: 10.1269/jrr.07123. PubMed DOI

Nikitaki Z., Velalopoulou A., Zanni V., Tremi I., Havaki S., Kokkoris M., Gorgoulis V.G., Koumenis C., Georgakilas A.G. Key biological mechanisms involved in high-LET radiation therapies with a focus on DNA damage and repair. Expert Rev. Mol. Med. 2022;24:e15. doi: 10.1017/erm.2022.6. PubMed DOI

Friedland W., Dingfelder M., Kundrát P., Jacob P. Track structures, DNA targets and radiation effects in the biophysical Monte Carlo simulation code PARTRAC. Mutat. Res. 2011;711:28–40. doi: 10.1016/j.mrfmmm.2011.01.003. PubMed DOI

Nikjoo H., Emfietzoglou D., Liamsuwan T., Taleei R., Liljequist D., Uehara S. Radiation track, DNA damage and response-a review. Rep. Prog. Phys. 2016;79:116601. doi: 10.1088/0034-4885/79/11/116601. PubMed DOI

Loeffler J.S., Durante M. Charged particle therapy—Optimization, challenges and future directions. Nat. Rev. Clin. Oncol. 2013;10:411–424. doi: 10.1038/nrclinonc.2013.79. PubMed DOI

Kirkby K.J., Kirkby N.F., Burnet N.G., Owen H., Mackay R.I., Crellin A., Green S. Heavy charged particle beam therapy and related new radiotherapy technologies: The clinical potential, physics and technical developments required to deliver benefit for patients with cancer. Br. J. Radiol. 2020;93:20200247. doi: 10.1259/bjr.20200247. PubMed DOI PMC

Haettner E., Iwase H., Schardt D. Experimental fragmentation studies with 12C therapy beams. Radiat. Prot. Dosim. 2006;122:485–487. doi: 10.1093/rpd/ncl402. PubMed DOI

Gunzert-Marx K., Iwase H., Schardt D., Simon R.S. Secondary beam fragments produced by 200 MeV u−1 12C ions in water and their dose contributions in carbon ion radiotherapy. New. J. Phys. 2008;10:075003. doi: 10.1088/1367-2630/10/7/075003. DOI

Fiedler F., Priegnitz M., Jülich R., Pawelke J., Crespo P., Parodi K., Pönisch F., Enghardt W. In-beam PET measurements of biological half-lives of 12C irradiation induced beta+-activity. Acta Oncol. 2008;47:1077–1086. doi: 10.1080/02841860701769743. PubMed DOI

Bellinzona E.V., Grzanka L., Attili A., Tommasino F., Friedrich T., Krämer M., Scholz M., Battistoni G., Embriaco A., Chiappara D., et al. Biological impact of target fragments on proton treatment plans: An analysis based on the current cross-section data and a full mixed field approach. Cancers. 2021;13:4768. doi: 10.3390/cancers13194768. PubMed DOI PMC

Horst F., Schardt D., Iwase H., Schuy C., Durante M., Weber U. Physical characterization of 3He ion beams for radiotherapy and comparison with 4He. Phys. Med. Biol. 2021;66:095009. doi: 10.1088/1361-6560/abef88. PubMed DOI

Kanazawa M., Kitagawa A., Kouda S., Nishio T., Torikoshi M., Noda K., Murakami T., Suda M., Tomitani T., Kanai T., et al. Application of an RI-beam for cancer therapy: In-vivo verification of the ion-beam range by means of positron imaging. Nucl. Phys. A. 2002;701:244–252. doi: 10.1016/S0375-9474(01)01592-5. DOI

Cucinotta F.A., Townsend L.W., Wilson J.W., Shinn J.L., Badhwar G.D., Dubey R.R. Light ion components of the galactic cosmic rays: Nuclear interactions and transport theory. Adv. Space Res. 1996;17:77–86. doi: 10.1016/0273-1177(95)00515-G. PubMed DOI

Norbury J.W., Slaba T.C. Space radiation accelerator experiments—The role of neutrons and light ions. Life Sci. Space Res. 2014;3:90–94. doi: 10.1016/j.lssr.2014.09.006. DOI

Adriani O., Barbarino G.C., Bazilevskaya G.A., Bellotti R., Boezio M., Bogomolov E.A., Bongi M., Bonvicini V., Bottai S., Bruno A., et al. Measurements of cosmic-ray hydrogen and helium isotopes with the PAMELA experiment. Astrophys. J. 2016;818:68. doi: 10.3847/0004-637X/818/1/68. DOI

Townsend L.W., Adams J.H., Blattnig S.R., Clowdsley M.S., Fry D.J., Jun I., McLeod C.D., Minow J.I., Moore D.F., Norbury J.W., et al. Solar particle event storm shelter requirements for missions beyond low Earth orbit. Life Sci. Space Res. 2018;17:32–39. doi: 10.1016/j.lssr.2018.02.002. PubMed DOI

Kutschera W. Accelerator mass spectrometry: State of the art and perspectives. Adv. Phys. X. 2016;1:570–595. doi: 10.1080/23746149.2016.1224603. DOI

Belli M., Cera F., Cherubini R., Goodhead D.T., Haque A.M.I., Ianzini F., Moschini G., Nikjoo H., Sapora O., Simone G., et al. Inactivation induced by deuterons of various LET in V79 cells. Radiat. Prot. Dosim. 1994;52:305–310. doi: 10.1093/oxfordjournals.rpd.a082205. DOI

Folkard M., Prise K.M., Vojnovic B., Newman H.C., Roper M.J., Michael B.D. Inactivation of V79 cells by low-energy protons, deuterons and helium-3 ions. Int. J. Radiat. Biol. 1996;69:729–738. doi: 10.1080/095530096145472. PubMed DOI

Bettega D., Calzolari P., Marchesini R., Noris Chiorda G.L., Piazzolla A., Tallone L., Cera F., Cherubini R., Dalla Vecchia M., Favaretto S., et al. Inactivation of C3H10T1/2 cells by low energy protons and deuterons. Int. J. Radiat. Biol. 1998;73:303–309. doi: 10.1080/095530098142400. PubMed DOI

Belli M., Cherubini R., Dalla Vecchia M., Dini V., Moschini G., Signoretti C., Simone G., Tabocchini M.A., Tiveron P. DNA DSB induction and rejoining in V79 cells irradiated with light ions: A constant field gel electrophoresis study. Int. J. Radiat. Biol. 2000;76:1095–1104. doi: 10.1080/09553000050111569. PubMed DOI

Barendsen G.W., Walter H.M., Fowler J.F., Bewley D.K. Effects of different ionizing radiations on human cells in tissue culture. III. Experiments with cyclotron-accelerated alpha-particles and deuterons. Radiat. Res. 1963;18:106–119. doi: 10.2307/3571430. PubMed DOI

Bird R.P., Rohrig N., Colvett R.D., Geard C.R., Marino S.A. Inactivation of synchronized Chinese Hamster V79 cells with charged-particle track segments. Radiat. Res. 1980;82:277–289. doi: 10.2307/3575379. PubMed DOI

Hei T.K., Chen D.J., Brenner D.J., Hall E.J. Mutation induction by charged particles of defined linear energy transfer. Carcinogenesis. 1988;9:1233–1236. doi: 10.1093/carcin/9.7.1233. PubMed DOI

Tommasino F., Friedrich T., Scholz U., Taucher-Scholz G., Durante M., Scholz M. A DNA double-strand break kinetic rejoining model based on the local effect model. Radiat. Res. 2013;180:524–538. doi: 10.1667/RR13389.1. PubMed DOI

Curtis S.B. Lethal and potentially lethal lesions induced by radiation—A unified repair model. Radiat. Res. 1986;10:252–270. doi: 10.2307/3576798. Erratum in Radiat. Res. 1989, 119, 584. PubMed DOI

Hawkins R.B. A microdosimetric-kinetic model for the effect of non-Poisson distribution of lethal lesions on the variation of RBE with LET. Radiat. Res. 2003;160:61–69. doi: 10.1667/RR3010. PubMed DOI

Lind B.K., Persson L.M., Edgren M.R., Hedlöf I., Brahme A. Repairable-conditionally repairable damage model based on dual Poisson processes. Radiat. Res. 2003;160:366–375. doi: 10.1667/0033-7587(2003)160[0366:RRDMBO]2.0.CO;2. PubMed DOI

Kundrát P. Detailed analysis of the cell-inactivation mechanism by accelerated protons and light ions. Phys. Med. Biol. 2006;51:1185–1199. doi: 10.1088/0031-9155/51/5/010. PubMed DOI

Friedrich T., Scholz U., Elsässer T., Durante M., Scholz M. Calculation of the biological effects of ion beams based on the microscopic spatial damage distribution pattern. Int. J. Radiat. Biol. 2012;88:103–107. doi: 10.3109/09553002.2011.611213. PubMed DOI

Friedland W., Schmitt E., Kundrát P., Dingfelder M., Baiocco G., Barbieri S., Ottolenghi A. Comprehensive track-structure based evaluation of DNA damage by light ions from radiotherapy-relevant energies down to stopping. Sci. Rep. 2017;7:45161. doi: 10.1038/srep45161. PubMed DOI PMC

Kundrát P., Friedland W., Becker J., Eidemüller M., Ottolenghi A., Baiocco G. Analytical formulas representing track-structure simulations on DNA damage induced by protons and light ions at radiotherapy-relevant energies. Sci. Rep. 2020;10:15775. doi: 10.1038/s41598-020-72857-z. PubMed DOI PMC

Kundrát P., Friedland W., Ottolenghi A., Baiocco G. Coupling radiation transport and track-structure simulations: Strategy based on analytical formulas representing DNA damage yields. Front. Phys. 2021;9:719682. doi: 10.3389/fphy.2021.719682. DOI

ICRU Report 49: Stopping Powers and Ranges for Protons and Alpha Particles. International Commission on Radiation Units and Measurements; Bethesda, MD, USA: 1993.

NIST—National Institute of Standards and Technology; Gaithersburg, MD, USA: [(accessed on 31 May 2022)]. PSTAR—Stopping-Power and Range Tables for Protons. Available online: https://physics.nist.gov/PhysRefData/Star/Text/PSTAR.html.

Friedland W., Kundrát P., Schmitt E., Becker J., Li W. Modeling DNA damage by photons and light ions over energy ranges used in medical applications. Radiat. Prot. Dosim. 2019;183:84–88. doi: 10.1093/rpd/ncy245. PubMed DOI

Kreipl M.S., Friedland W., Paretzke H.G. Time- and space-resolved Monte Carlo study of water radiolysis for photon, electron and ion irradiation. Radiat. Env. Biophys. 2009;48:11–20. doi: 10.1007/s00411-008-0194-8. PubMed DOI

Friedland W., Jacob P., Kundrát P. Stochastic simulation of DNA double-strand break repair by non-homologous end joining based on track structure calculations. Radiat. Res. 2010;173:677–688. doi: 10.1667/RR1965.1. PubMed DOI

Friedland W., Kundrát P. Track structure based modelling of chromosome aberrations after photon and alpha-particle irradiation. Mutat. Res. 2013;756:213–223. doi: 10.1016/j.mrgentox.2013.06.013. PubMed DOI

Friedland W., Kundrát P. Chromosome aberration model combining radiation tracks, chromatin structure, DSB repair and chromatin mobility. Radiat. Prot. Dosim. 2015;166:71–74. doi: 10.1093/rpd/ncv174. PubMed DOI

Friedland W., Kundrát P., Jacob P. Track structure calculations on hypothetical subcellular targets for the release of cell-killing signals in bystander experiments with medium transfer. Radiat. Prot. Dosim. 2011;143:325–329. doi: 10.1093/rpd/ncq401. PubMed DOI

Kundrát P., Friedland W. Track structure calculations on intracellular targets responsible for signal release in bystander experiments with transfer of irradiated cell-conditioned medium. Int. J. Radiat. Biol. 2012;88:98–102. doi: 10.3109/09553002.2011.595874. PubMed DOI

Friedland W., Schmitt E., Kundrát P., Baiocco G., Ottolenghi A. Track-structure simulations of energy deposition patterns to mitochondria and damage to their DNA. Int. J. Radiat. Biol. 2019;95:3–11. doi: 10.1080/09553002.2018.1450532. PubMed DOI

Dingfelder M., Inokuti M., Paretzke H.G. Inelastic-collision cross sections of liquid water for interactions of energetic protons. Radiat. Phys. Chem. 2000;59:255–275. doi: 10.1016/S0969-806X(00)00263-2. DOI

Friedland W., Dingfelder M., Jacob P., Paretzke H.G. Calculated DNA double-strand break and fragmentation yields after irradiation with He ions. Radiat. Phys. Chem. 2005;72:279–286. doi: 10.1016/j.radphyschem.2004.05.053. DOI

Schmitt E., Friedland W., Kundrát P., Dingfelder M., Ottolenghi A. Cross-section scaling for track structure simulations of low-energy ions in liquid water. Radiat. Prot. Dosim. 2015;166:15–18. doi: 10.1093/rpd/ncv302. PubMed DOI

ICRU Report 36: Microdosimetry. International Commission on Radiation Units and Measurements; Bethesda, MD, USA: 1983.

Mapping neutron biological effectiveness for DNA damage induction as a function of incident energy and depth in a human sized phantom