Abstract
Accurate dosimetric calculations at cellular and sub-cellular levels are crucial to obtain an increased understanding of the interactions of ionizing radiation with a cell and its nucleus and cytoplasm. Ion microbeams provide a superior opportunity to irradiate small biological samples, e.g., DNA, cells, and to compare their response to computer simulations. However, the phantoms used to simulate small biological samples at cellular levels are often simplified as simple volumes filled with water. As a first step to improve the situation in comparing measurements of cell response to ionizing radiation with model calculations, a realistic voxel model of a KB cell was constructed and used together with an already constructed geometry and tracking 4 (GEANT4) model of the horizontal microbeam line of the Centre d’Etudes Nucléaires de Bordeaux-Gradignan (CENBG) 3.5 MV Van de Graaf accelerator at the CENBG, France. The microbeam model was then implemented into GEANT4 for simulations of the average number of particles hitting an irradiated cell when a specified number of particles are produced in the beam line. The result shows that when irradiating the developed voxel model of a KB cell with 200 α particles, with a nominal energy of 3 MeV in the beam line and 2.34 MeV at the cell entrance, 100 particles hit the cell on average. The mean specific energy is 0.209 ± 0.019 Gy in the nucleus and 0.044 ± 0.001 Gy in the cytoplasm. These results are in agreement with previously published data, which indicates that this model could act as a reference model for dosimetric calculations of radiobiological experiments, and that the proposed method could be applied to build a cell model database.
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Agostinelli S, Allison J, Amako K, Apostolakis J, Araujj H, Arce P, Asai M, Axen D, Banerjee S, Barrand G, Behnel F, Bellagamba L, Boudreau J, Broglia L, Brunengo A, Burkhard H, Chauvie S, Chuma J, Chytracek R, Cooperman G, Cosmo G, Degtyarenko P, Dell’Acqua A, Depaola G, Dietrich D, Enami R, Feliciello A, Ferguson C, Fesefeldt H, Folger G, Foppiano F, Fortias A, Garelli S, Giani S, Giannitrapani R, Gibin D, Gómez Cadenas JJ, González I, Gracia Abril G, Greeniaus G, Greiner W, Grichine V, Grossheim A, Guatelli S, Gumplinger P, Hamatsu R, Hashimoto K, Hasui H, Heikkinen A, Howard A (2003) GEANT4—a simulation toolkit. Nucl Instrum Methods Phys Res A 506:250–303
Alard JP, Bodez V, Tchirko A, Tchirkov A, Nénot ML, Arnold J, Crespin S, Rapp M, Verrelle P, Dionet C (2002) Simulation of neutron interactions at the single-cell level. Radiat Res 158:650–656
Allison J, Amako K, Apostolakis J, Araujo H, Dubois PA, Asai M, Barrand G, Capra R, Chauvie S, Chytracek R, Cirrone GAP, Cooperman G, Cosmo G, Cuttone G, Daquino GG, Donszelmann M, Dressel M, Folger G, Foppiano F, Generowicz J, Grichine V, Guatelli S, Gumplinger P, Heikkinen A, Hrivnacova I, Howard A, Incerti S, Ivanchenko V, Johnson T, Jones F, Koi T, Kokoulin R, Kossov M, Kurashige H, Lara V, Larsson S, Lei F, Link O, Longo F, Maire M, Mantero A, Mascialin B, McLaren I, Lorenzo PM, Minamimoto K, Murakami K, Nieminen P, Pandola L, Parlati S, Peralta L, Perl J, Pfeiffer A, Pia MG, Ribon A, Rodrigues P, Russo G, Sadilov S, Santin G, Sasaki T, Smith D, Starkov N, Tanaka S, Tcherniaev E, Tome B, Trindade A, Truscott P, Urban L, Verderi M, Walkden A, Wellisch JP, Williams DC, Wright D, Yoshida H (2006) GEANT4 developments and applications. IEEE Trans Nucl Sci 53:270–278
Antcheva I, Ballintijn M, Bellenot B (2011) ROOT—A C++ framework for petabyte data storage, statistical analysis and visualization. Comput Phys Commun 182:1384–1385
Archambault L, Beaulieu L, Carrier JF (2003) Overview of GEANT4 applications in medical physics. Nucl Sci Symp Conf Rec 3:1743–1745
Arne M (1986) Dosimetry for radiation processing. Int J Radiat Appl Instrum Part C Radiat Phys Chem 28:521–529
Barberet P, Vianna F, Karamitros M, Brun T, Gordillo N, Moretto P, Incerti S, Seznec H (2012) Monte-Carlo dosimetry on a realistic cell monolayer geometry exposed to alpha-particle. Phys Med Biol 57:2189–2207
Barcellos MH, Brooks AL (2001) Extracellular signaling through the micro-environment: a hypothesis relating carcinogenesis, bystander effects, and genomic instability. Radiat Res 156:618–627
Baverstock K, Belyakov OV (2005) Classical radiation biology, the bystander effect and paradigms: a reply. Hum Exp Toxicol 24:537–542
Beaton LA, Burn TA, Stocki TJ, Chauhan V, Wilkins RC (2011) Development and characterization of an in vitro alpha radiation exposure system. Phys Med Biol 56:3645–3658
Belyakov OV, Malcolmson AM, Folkard M, Prise KM, Michael BD (2001) Direct evidence for a bystander effect of ionizing radiation in primary human fibroblasts. Br J Cancer 84:674–679
Belyakov OV, Folkard M, Prise KM, Michael BD, Mothersill C (2002) Non-targeted effects of radiation: applications for radiation protection and contribution to LNT discussion. In: Proceedings of the European IRPA congress 2002 “Towards harmonisation of radiation protection in Europe”. Florence, Italy, 8–11 October 2002
Blau M, Altenburger K (1922) Über einige Wirkungen von Strahlen. II. Z Phys 12:315–329
Chauvie S, Francis Z, Guatelli S, Incerti S, Mascialino B, Moretto P, Nieminen P, Pia MG (2007) GEANT4 physics processes for microdosimetry simulation: design foundation and implementation of the first set of models. IEEE Trans Nucl Sci 54:2619–2628
Collins TJ (2007) ImageJ for microscopy. Biotechniques 43:25–30
Freudenber R, Wendisch M, Kotzerke J (2011) GEANT4-simulations for cellular dosimetry in nuclear medicine. Z Med Phys 21:281–289
Incerti S, Baldacchino G, Bernal M, Capra R, Champion C, Francis Z, Gueye P, Mantero A, Mascialino B, Moretto P, Nieminen P, Villagrasa C, Zacharatou C (2010) The GEANT4-DNA project. Int J Model Simul Sci Comput 1:157–158
Incerti S, Barberet Ph, Villeneuve R, Aguer P, Gontier E, Michelet-Habchi C, Moretto P, Nguyen DT, Pouthier T, Smith RW (2004) Simulation of cellular irradiation with the CENBG microbeam line using GEANT4. IEEE Trans Nucl Sci 51:1395–1401
Incerti S, Gault N, Habchi C, Lefaix JL, Moretto Ph, Poncy JL, Pouthier T, Seznec H (2006) A comparison of cellular irradiation techniques with alpha particles using the GEANT4 Monte Carlo simulation toolkit. Radiat Prot Dosim 122(1–4):327–329
Incerti S, Seznec H, Simon M, Barberet Ph, Habchi C, Moretto Ph (2009) Monte Carlo dosimetry for targeted irradiation of individual cells using a microbeam facility. Radiat Prot Dosim 133:2–11
Ivanov VI (1973) II All-union conference on microdosimetry. Sov Atomic Energy 35:954–955
Iyer R, Lehnert BE, Svensson R (2000) Factors underlying the cell growth-related bystander responses to alpha particles. Cancer Res 60:1290–1297
Karamitros M, Mantero A, Incerti S (2011) Modeling radiation chemistry in the GEANT4 toolkit. Prog Nucl Sci Technol 2:503–508
Lea DE (1946) Actions of radiations on living cells. Cambridge University Press, Cambridge
Lett JT, Stacey KA, Alexander P (1961) Cross-linking of dry deoxyribonucleic acids by electrons. Radiat Res 14:349–362
Lewis DA, Mayhugh BM, Qin Y, Trott K, Mendonca MS (2001) Production of delayed death and neoplastic transformation in CGL1 cells by radiation-induced bystander effects. Radiat Res 156:251–258
Lorimore SA, Kadhim MA, Pocock DA, Papworth D, Stevens DL, Goodhead DT, Wright EG (1998) Chromosomal instability in the descendants of unirradiated surviving cells after a-particle irradiation. Proc Natl Acad Sci 95(5730–5733):8
Marshell M, Gibson JA, Holt PD (1970) An analysis of the target theory of Lea with modern data. Int J Radiat Biol Relat Stud Phys Chem Med 18(2):127–138
Matile P (1971) Vacuoles, lysosomes of neurospora. Cytobiologie 3:324–330
Matsumoto H, Hayashi S, Hatashita M (2001) Induction of radioresistance by a nitric oxide-mediated bystander effect. Radiat Res 155:387–396
Miller JH, Resat MS, Metting NF, Wei K, Wilson WE (2000) Monte Carlo simulation of single-cell irradiation by an electron microbeam. Radiat Environ Biophys 39:173–177
Nagasawa H, Hayashi S, Hatashita M, Ohnishi K, Shioura H, Ohtsubo T, Kitai R, Ohnishi T, Kano E (1999) Unexpected sensitivity to the induction of mutations by very low doses of alpha-particle radiation: evidence for a bystander effect. Radiat Res 152:552–557
Puck TT, Marcus PI (1956) Action of Xrays on mammalian cells. J Exp Med 103:653–666
Rademakers F, Brun R (1998) ROOT: an object-oriented data analysis framework. Nucl Instrum Meth Phys Res A389:81–86
Sawant SG, Pehrson GR, Geard CR, Brenner DJ, Hall EJ (2001) The bystander effect in radiation oncogenesis. Radiat Res 155:397–401
Sutton ML, Hendry JH (1991) Applied Radiobiology. In: Easson EC, Pointon RCS (eds) The radiotherapy of malignant disease. Springer, London, pp 33–55
Tea-Yuan H, Chin-Yuan H (1994) On the joint distribution of Grubbs’ statistics. Ann Inst Stat Math 46:769–775
Ward J (1999) New paradigms for low-dose radiation response. In: Proceedings of the American statistical association conference on radiation and health. Radiat Res 151:92–117
Wykoff CC, Beasley NJ, Watson PH, Turner KJ, Pastorek J, Sibtain A, Wilson GD, Turley H, Talks KL, Maxwell PH, Pugh CW, Ratcliffe PJ, Harris AL (2000) Hypoxia-inducible expression of tumor-associated carbonic anhydrases. Cancer Res 60:7075–7083
Zhou H, Randers-Pehrson G, Waldren CA, Vannais D, Hall EJ, Hei TK (2000) Induction of a bystander mutagenic effect of alpha particles in mammalian cells. PNAS 97:2099–2104
Acknowledgments
We appreciate the help of Dr. B. Li during the biological experiments. We also acknowledge the support of Dr. S. Incerti for helping us with the GEANT4 calculations. This work was funded by PAPD (A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions).
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Sihver, L., Ni, J., Sun, L. et al. Voxel model of individual cells and its implementation in microdosimetric calculations using GEANT4. Radiat Environ Biophys 53, 571–579 (2014). https://doi.org/10.1007/s00411-014-0549-2
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DOI: https://doi.org/10.1007/s00411-014-0549-2