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Isochore Nuclear Geometry for modeling the radiation-induced DNA damage toplogy

hal.structure.identifierLaboratoire de dosimétrie des rayonnements ionisants [IRSN/PSE-SANTE/SDOS/LDRI]
dc.contributor.authorTHIBAUT, Yann
hal.structure.identifierLaboratoire de dosimétrie des rayonnements ionisants [IRSN/PSE-SANTE/SDOS/LDRI]
dc.contributor.authorVILLAGRASA, Carmen
hal.structure.identifierCentre d'Etudes Nucléaires de Bordeaux Gradignan [CENBG]
dc.contributor.authorINCERTI, Sébastien
hal.structure.identifierLaboratoire de dosimétrie des rayonnements ionisants [IRSN/PSE-SANTE/SDOS/LDRI]
dc.contributor.authorPERROT, Yann
dc.date.issued2021
dc.date.conference2021-11-26
dc.description.abstractEnResearch dealing with a better understanding of the origin and mechanisms behind deleterious effects of radiation therapies on healthy tissues is a crucial topic in radiation protection. These side effects can result from damage to the nuclear DN molecule of healthy cells exposed to ionizing radiation during treatment. In order to better describe the molecular mechanisms underlying these undesirable effects, our laboratory is developing a simulation chain to calculate early radiation-induced damage to DNA for different beam qualities. Studies at this scale require a nanodosimetric description of energy deposits, enabled by the Geant4-DNA Monte-Carlo toolkit, coupled to DNA geometrical models with molecular precision. The current version of this simulation chain allows a realistic modeling of the topology of DNA damage (number of DSBs, complexity, spatial distribution) at the cellular scale. Up to now the geometries of the cell genome used in the simulation take into account chromatin compaction by implementing 52% euchromatin and 48% heterochromatin, distributed randomly along the genome which makes it possible to account for experimental observations.To improve the quality of these DNA damage results, a more realistic nuclear geometric model is presented. It is based on the isochoric biological model carrying out a mapping of the genome, by segmenting it into portions of 1 Mbp in our application. Each of these segments is then classified into one of five isochoric families (L1, L2, H1, H2, H3) based on the ratio of CG base pairs it contains and related to different degrees of chromatin fiber compaction. To evaluate the influence of these new geometric models on the topology of radiation-induced DNA damage, simulations are performed for perpendicular irradiations of protons (4.28 keV.μm-1, 19.51 keV.μm-1, 43.24 keV.μm-1).The DNA damage results obtained for a cell using the new geometric isochoric model are compared with those obtained previously with a random distribution of chromatin compaction respecting the same overall heterochromatin / euchromatin ratio. This comparison indicates that the organization of chromatin fiber compaction in accordance with the isochore theory of our new model has an impact via different mechanisms on the number and type of calculated damages.
dc.language.isoen
dc.rights.urihttp://hal.archives-ouvertes.fr/licences/copyright/
dc.title.enIsochore Nuclear Geometry for modeling the radiation-induced DNA damage toplogy
dc.typeAutre communication scientifique (congrès sans actes - poster - séminaire...)
dc.subject.halPhysique [physics]
bordeaux.countryFR
bordeaux.conference.cityCAEN
bordeaux.peerReviewedoui
hal.identifierhal-03505857
hal.version1
hal.invitednon
hal.proceedingsnon
hal.conference.end2021-11-30
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-03505857v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.date=2021&rft.au=THIBAUT,%20Yann&VILLAGRASA,%20Carmen&INCERTI,%20S%C3%A9bastien&PERROT,%20Yann&rft.genre=conference


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