Advances in accelerator technology, which have enabled conforming radiotherapy with charged hadronic species, have brought benefits as well as potential new risks to patients. To better understand the effects of ionizing radiation on tumor and surrounding tissue, it is important to investigate and quantify the relationship between energy deposition at the nanometric scale and the initial biological events. Monte Carlo track structure simulation codes provide a powerful tool for investigating this relationship; however, their success and reliability are dependent on their improvement and development accordingly to the dedicated biological data to which they are challenged. For this aim, a microbeam facility that allows for fluence control, down to one ion per cell nucleus, was used to evaluate relative frequencies of DNA damage after interaction between the incoming ion and DNA according to radiation quality. Primary human cells were exposed to alpha particles of three different energies with respective linear energy transfers (LETs) of approximately 36, 85 or 170 keV·µm–1 at the cells' center position, or to protons (19 keV·µm–1). Statistical evaluation of nuclear foci formation (53BP1/γ-H2AX), observed using immunofluorescence and related to a particle traversal, was undertaken in a large population of cell nuclei. The biological results were adjusted to consider the factors that drive the experimental uncertainties, then challenged with results using Geant4-DNA code modeling of the ionizing particle interactions on a virtual phantom of the cell nucleus with the same mean geometry and DNA density as the cells used in our experiments. Both results showed an increase of relative frequencies of foci (or simulated DNA damage) in cell nuclei as a function of increasing LET of the traversing particles, reaching a quasi-plateau when the LET exceeded 80–90 keV·µm–1. For the LET of an alpha particle ranging from 80–90 to 170 keV·µm–1, 10–30% of the particle hits did not lead to DNA damage inducing 53BP1 or γ-H2AX foci formation.
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1 June 2019
Research Article|
April 25 2019
From Energy Deposition of Ionizing Radiation to Cell Damage Signaling: Benchmarking Simulations by Measured Yields of Initial DNA Damage after Ion Microbeam Irradiation
Géraldine Gonon;
Géraldine Gonon
1
aRadiobiology of Accidental Exposure Laboratory
1Address for correspondence: Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratory of Radiobiology of Acccidental Exposures (LRAcc), 31 Avenue de la Division Leclerc, Fontenay-aux-Roses, France 92262; email: geraldine.gonon@irsn.fr.
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Carmen Villagrasa;
Carmen Villagrasa
bIonizing Radiation Dosimetry Laboratory
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Pascale Voisin;
Pascale Voisin
aRadiobiology of Accidental Exposure Laboratory
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Sylvain Meylan;
Marta Bueno;
Marta Bueno
bIonizing Radiation Dosimetry Laboratory
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Mohamed Amine Benadjaoud;
Mohamed Amine Benadjaoud
cRadiobiology and Regenerative Medicine Research Service, Direction of Human Health, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Fontenay-aux-Roses, France
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Nicolas Tang;
Nicolas Tang
bIonizing Radiation Dosimetry Laboratory
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Frank Langner;
Frank Langner
dDepartment 6.5 Radiation Effects, Physikalisch-Technische Bundesanstalt (PTB), Braunschweig, Germany
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Hans Rabus;
Hans Rabus
dDepartment 6.5 Radiation Effects, Physikalisch-Technische Bundesanstalt (PTB), Braunschweig, Germany
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Joan-Francesc Barquinero;
Joan-Francesc Barquinero
3
aRadiobiology of Accidental Exposure Laboratory
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Ulrich Giesen;
Ulrich Giesen
dDepartment 6.5 Radiation Effects, Physikalisch-Technische Bundesanstalt (PTB), Braunschweig, Germany
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Gaëtan Gruel
Gaëtan Gruel
aRadiobiology of Accidental Exposure Laboratory
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Radiat Res (2019) 191 (6): 566–584.
Article history
Received:
December 14 2018
Accepted:
March 13 2019
Citation
Géraldine Gonon, Carmen Villagrasa, Pascale Voisin, Sylvain Meylan, Marta Bueno, Mohamed Amine Benadjaoud, Nicolas Tang, Frank Langner, Hans Rabus, Joan-Francesc Barquinero, Ulrich Giesen, Gaëtan Gruel; From Energy Deposition of Ionizing Radiation to Cell Damage Signaling: Benchmarking Simulations by Measured Yields of Initial DNA Damage after Ion Microbeam Irradiation. Radiat Res 1 June 2019; 191 (6): 566–584. doi: https://doi.org/10.1667/RR15312.1
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