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Poster De Conférence Année : 2019

Biological measure of DNA damage after single-ion microbeam irradiation and Monte Carlo simulations

Résumé

Background/Aim : 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, according to how energy is deposited within cells by ionizing particle tracks. Monte Carlo track structure simulation provides a powerful tool for investigating such relation. However, the reliability of simulation results can only be assessed by comparison with dedicated biological data. Methods : Primary human cells were exposed, with single-ion microbeam facility, to α particles and protons of different energies with LETs ranging from 19 to 170 keV·μm-1 at the cells’ center position. Statistical evaluation of nuclear foci formation (53BP1/γ-H2AX) 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 Geant4-DNA simulations results. Such simulations model 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. Conclusions : These findings will allow for a better comprehension of the relationship between the topology of energy deposition from particles of different LET and early cell damage. They will also help obtain an accurate estimate of the probability of particle interaction to induce foci formation at DNA damage sites. Work carried out within EMRP (European Metrology Research Programme) JRP-SIB06 BioQuaRT (Biologically weighted Quantities in RadioTherapy).
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hal-02635559 , version 1 (27-05-2020)

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  • HAL Id : hal-02635559 , version 1

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Geraldine Gonon, Carmen Villagrasa, Pascale Voisin, Sylvain Meylan, Mohamedamine Benadjaoud, et al.. Biological measure of DNA damage after single-ion microbeam irradiation and Monte Carlo simulations. 16th International Congress of Radiation Research ICRR 2019, Aug 2019, MANCHESTER, France. 2019. ⟨hal-02635559⟩
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