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Communication Dans Un Congrès Année : 2019

DNA damage yields after microbeam irradiation and comparison to MC simulations

Résumé

Introduction The growing use of hadrons in oncology entails the need to establish more specific dosimetry concepts adapted to their biological efficacy. This requires more information on the likelihood of subcellular effects, mainly DNA damage (double-strand breaks), according to the details of how energy is deposited within cells by ionizing particle tracks. Monte Carlo track structure simulation provides a powerful tool for investigating this relation. However, the reliability of simulation results can only be assessed by comparison with dedicated biological data. Methods Experiments were conducted on a single-ion microbeam. Primary human cells were exposed to α particles of different energies with respective LETs of about 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 by immunofluorescence and related to a particle traversal was undertaken in a large population of cell nuclei. The biological results were adjusted for factors leading to experimental bias and compared with results from Geant4-DNA simulations modeling the ionizing particle interactions on a virtual phantom of the cell nucleus with the same geometry and DNA density as the cells used in the experiments. Results Observed relocation/modification of DNA damage signaling proteins and simulations both show an initial increase of the relative frequency of induction of DNA damage with increasing LET of the projectile. For α particles of LET ranging from 80-90 to 170 keV·μm-1, a constant DNA damage-induction frequency was found where 10-30% of the particle traversals did not lead to foci formation indicating DNA damage. Conclusions These findings allow studying the relationship between the topology of energy deposition from particles of different LET and early cell damaging, obtaining an accurate estimate of the probability of interactions which induce foci formation after DNA damage.
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hal-02748798 , version 1 (20-08-2020)

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Copyright (Tous droits réservés)

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  • HAL Id : hal-02748798 , version 1

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Geraldine Gonon, Pascale Voisin, Joan Francesc Barquinero, Carmen Villagrasa, Gaetan Gruel, et al.. DNA damage yields after microbeam irradiation and comparison to MC simulations. 3rd International Conference on Dosimetry and its Applications (ICDA-3), ICDA-3, May 2019, LISBONNE, Portugal. ⟨hal-02748798⟩
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