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&. .. Adn, 167 5.1.1 Jonction d'extrémités non-homologues (NHEJ), Les voies de réparation des dommages à l

, 2.2.1 Le « Two-lesion kinetic model » (TLK), Les modèles d'extension vers les effets tardifs

. .. , 3 BIANCA (Biophysical analysis of cell death and chromosome aberrations)

L. Iv and T. .. Du-modèle, 3.2 Application du modèle TLK pour le calcul des courbes de survie cellulaire, Choix des modèles paramétriques : application

. .. Conclusions-du-chapitre,

. .. Références,

. Nguyen, et ne peut donc prédire à elle seule, un effet biologique. Un modèle radiobiologique intégrant en plus de la mort cellulaire, l'état (phénotype) des cellules survivantes permettrait de dépasser les limites actuelles de l'EBR. Dans le programme ROSIRIS, les effets tardifs additionnels à la mort cellulaire sont considérés comme par exemple, le nombre de foyers ?-H2AX persistants, le phénomène de sénescence (arrêt irréversible du cycle cellulaire) etc. Cela mènerait donc à l'apparition d'une EBR « multiparamétrique » dont les données expérimentales devront être reliées aux données simulées afin d'établir leurs éventuelles relations. L'utilisation conjointe des simulations Monte-Carlo pour le calcul des dommages et de modèles paramétriques intégrant les différentes finalités biologiques et leurs mesures expérimentales, Chapitre 5 -Extension de la simulation vers les effets biologiques tardifs Geant4-DNA comme données d'entrée de ces différents modèles afin de pouvoir évaluer leur compatibilité, 2018.

, ce stade, c'est-à-dire, que l'algorithme de clusterisation DBScan n'est pas utilisé

, ADN) et lorsqu'un SB se trouve à moins de 10 bp de ce DSB, il n'est pas pris en compte dans celui-ci. Egalement, notons que contrairement au LEM IV, nous avons utilisé tardifs et permettra notamment, d'établir d'autres modèles paramétriques pour d'autres finalités biologiques. Ces outils seront utilisés afin de pouvoir établir la chaîne de causalité entre les dommages à l'ADN obtenus par simulation et l'évolution du nombre de foyers ?-H2AX, de foyers persistants, la sénescence, la mort cellulaire. Tout cela sera pris en compte dans une EBR « multiparamétrique » (Cf. Section 5.3) afin de mieux étudier les effets d, Les DSBs sont alors tous « simples » (deux SB séparés par moins de 10 bp et situés sur des brins opposés de l'

, Chapitre 5 -Extension de la simulation vers les effets biologiques tardifs

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. Lampe, ainsi que dans la poursuite de la contribution de l'IRSN aux collaborations Geant4 et Geant4-DNA. La première partie de ce travail de thèse a consisté tout d'abord, à modifier la partie chimique de la chaîne de simulation au niveau des réactions chimiques considérées. De nouvelles réactions ont été prises en compte entre les différents radicaux libres et l'ADN en suivant l'approche adoptée par, Le travail de thèse présenté dans ce manuscrit s'encadre donc dans la continuité de ce sujet à l'IRSN (projet ROSIRIS), 2018.

;. Puis and . Tang, Pour cela, des simulations d'irradiations avec des ions (protons et alphas) ont été effectuées sur trois modèles de noyaux de cellules humaines développés avec DnaFabric lors de la thèse précédente [MEYLAN, Ces modèles correspondent à des noyaux de fibroblastes, de lymphocytes et de cellules endothéliales présentant des caractéristiques morphologiques différentes. Il a été montré Conclusions et perspectives, 2016.

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N. Tang, M. Bueno, and S. Meylan, Influence of chromatin compaction on simulated early radiation-induced DNA damage using Geant4-DNA, Medical Physics, vol.46, issue.3, pp.1501-1511, 2019.
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N. Tang, M. Bueno, and S. Meylan, Simulation of early radiation-induced DNA damage on different types of cell nuclei, Radiation Protection Dosimetry, vol.183, issue.1-2, pp.26-31, 2019.
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G. Gonon, C. Villagrasa, P. Voisin, S. Meylan, M. Bueno et al., From Energy Deposition of Ionizing Radiation to Cell Damage Signaling: Benchmarking Simulations by Measured Yields of Initial DNA Damage after Ion Microbeam Irradiation, Radiation Research, vol.191, issue.6, pp.566-584, 2019.
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N. Tang, M. Bueno, S. Meylan, S. Incerti, H. N. Tran et al., Influence of chromatin compaction on simulated early radiation-induced DNA damage using Geant4-DNA, Med Phys, vol.46, issue.3, pp.1501-1511, 2019.
URL : https://hal.archives-ouvertes.fr/hal-02097397

N. Tang, M. Bueno, S. Meylan, S. Incerti, I. Clairand et al., Simulation of early radiationinduced DNA damage on different types of cell nuclei, Radiat Prot Dosimetry, vol.183, issue.1-2, pp.26-31, 2019.
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A. Freneau, M. Santos, P. Voisin, N. Tang, M. Bueno et al., Relation between DNA double-strand breaks and energy spectra of secondary electrons produced by different X-ray energies, Int J Radiat Biol, pp.1-10, 2018.

S. Incerti, I. Kyriakou, M. A. Bernal, M. C. Bordage, Z. Francis et al., Geant4-DNA example applications for track structure simulations in liquid water: A report from the Geant4-DNA Project, Medical Physics, vol.45, issue.8, pp.722-739, 2018.
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S. Meylan, S. Incerti, M. Karamitros, N. Tang, M. Bueno et al., Simulation of early DNA damage after the irradiation of a fibroblast cell nucleus using Geant4-DNA, Scientific Reports, vol.7, issue.1, p.11923, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01703528

N. Tang, M. Bueno, S. Meylan, Y. Perrot, H. N. Tran et al., Assessment of the biological response of endothelial cells irradiated with 40 kVp, 220 kVp and 4 MV X-rays by means of micro and nanodosimetric calculations, International Journal of Molecular Sciences

, Communications internationales

N. Tang, M. Bueno, S. Meylan, S. Incerti, C. Villagrasa et al., Influence of chromatin compaction on simulated early radiation-induced DNA damage using Geant4-DNA, Physics-Medicine-Biology frontier, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02097397

N. Tang, M. Bueno, S. Meylan, S. Incerti, C. Villagrasa et al., Influence of chromatin compaction on early radiation-induced DNA damage. Oral au 15 th International Workshop on Radiation damage to DNA, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02097397

N. Tang, M. Bueno, S. Meylan, I. Clairand, S. Incerti et al., Simulation of early radiation-induced DNA damage on different types of cell nuclei, th International Symposium on Microdosimetry, Venise, Italie, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02144332

N. Tang, M. Bueno, S. Meylan, I. Clairand, S. Incerti et al., Simulation of early radiation-induced DNA damage on different types of cell nuclei. Oral au 11 th Cancéropôle Grand-Ouest Workshop on Prediction and Modeling of response to Molecular and External Radiotherapies, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02144332

N. Tang, S. Meylan, F. Ballarini, I. Clairand, S. Incerti et al., Early DNA damage in a CHO cell nucleus after proton irradiation, Poster au 13 th Symposium on Neutron and Ion Dosimetry, Cracovie, Pologne. Prix : N. Tang, Novembre 2017, Young Investigator Award, 17 th International Symposium on Microdosimetry, 2017.

N. Tang, Travel Grant Award, 11 th Cancéropôle Grand-Ouest Workshop on Prediction and Modeling of response to Molecular and External Radiotherapies, EURADOS support for conference fees, 13 th Symposium on Neutron and Ion Dosimetry, 2017.