Cargando…
Nanodosimetric Calculations of Radiation-Induced DNA Damage in a New Nucleus Geometrical Model Based on the Isochore Theory
Double-strand breaks (DSBs) in nuclear DNA represents radiation-induced damage that has been identified as particularly deleterious. Calculating this damage using Monte Carlo track structure modeling could be a suitable indicator to better assess and anticipate the side-effects of radiation therapy....
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998209/ https://www.ncbi.nlm.nih.gov/pubmed/35409128 http://dx.doi.org/10.3390/ijms23073770 |
_version_ | 1784684887595286528 |
---|---|
author | Thibaut, Yann Tang, Nicolas Tran, Hoang Ngoc Vaurijoux, Aurélie Villagrasa, Carmen Incerti, Sébastien Perrot, Yann |
author_facet | Thibaut, Yann Tang, Nicolas Tran, Hoang Ngoc Vaurijoux, Aurélie Villagrasa, Carmen Incerti, Sébastien Perrot, Yann |
author_sort | Thibaut, Yann |
collection | PubMed |
description | Double-strand breaks (DSBs) in nuclear DNA represents radiation-induced damage that has been identified as particularly deleterious. Calculating this damage using Monte Carlo track structure modeling could be a suitable indicator to better assess and anticipate the side-effects of radiation therapy. However, as already demonstrated in previous work, the geometrical description of the nucleus and the DNA content used in the simulation significantly influence damage calculations. Therefore, in order to obtain accurate results, this geometry must be as realistic as possible. In this study, a new geometrical model of an endothelial cell nucleus and DNA distribution according to the isochore theory are presented and used in a Monte Carlo simulation chain based on the Geant4-DNA toolkit. In this theory, heterochromatin and euchromatin compaction are distributed along the genome according to five different families (L1, L2, H1, H2, and H3). Each of these families is associated with a different hetero/euchromatin rate related to its compaction level. In order to compare the results with those obtained using a previous nuclear geometry, simulations were performed for protons with linear energy transfers (LETs) of 4.29 keV/µm, 19.51 keV/µm, and 43.25 keV/µm. The organization of the chromatin fibers at different compaction levels linked to isochore families increased the DSB yield by 6–10%, and it allowed the most affected part of the genome to be identified. These new results indicate that the genome core is more radiosensitive than the genome desert, with a 3–8% increase in damage depending on the LET. This work highlights the importance of using realistic distributions of chromatin compaction levels to calculate radio-induced damage using Monte Carlo simulation methods. |
format | Online Article Text |
id | pubmed-8998209 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89982092022-04-12 Nanodosimetric Calculations of Radiation-Induced DNA Damage in a New Nucleus Geometrical Model Based on the Isochore Theory Thibaut, Yann Tang, Nicolas Tran, Hoang Ngoc Vaurijoux, Aurélie Villagrasa, Carmen Incerti, Sébastien Perrot, Yann Int J Mol Sci Article Double-strand breaks (DSBs) in nuclear DNA represents radiation-induced damage that has been identified as particularly deleterious. Calculating this damage using Monte Carlo track structure modeling could be a suitable indicator to better assess and anticipate the side-effects of radiation therapy. However, as already demonstrated in previous work, the geometrical description of the nucleus and the DNA content used in the simulation significantly influence damage calculations. Therefore, in order to obtain accurate results, this geometry must be as realistic as possible. In this study, a new geometrical model of an endothelial cell nucleus and DNA distribution according to the isochore theory are presented and used in a Monte Carlo simulation chain based on the Geant4-DNA toolkit. In this theory, heterochromatin and euchromatin compaction are distributed along the genome according to five different families (L1, L2, H1, H2, and H3). Each of these families is associated with a different hetero/euchromatin rate related to its compaction level. In order to compare the results with those obtained using a previous nuclear geometry, simulations were performed for protons with linear energy transfers (LETs) of 4.29 keV/µm, 19.51 keV/µm, and 43.25 keV/µm. The organization of the chromatin fibers at different compaction levels linked to isochore families increased the DSB yield by 6–10%, and it allowed the most affected part of the genome to be identified. These new results indicate that the genome core is more radiosensitive than the genome desert, with a 3–8% increase in damage depending on the LET. This work highlights the importance of using realistic distributions of chromatin compaction levels to calculate radio-induced damage using Monte Carlo simulation methods. MDPI 2022-03-29 /pmc/articles/PMC8998209/ /pubmed/35409128 http://dx.doi.org/10.3390/ijms23073770 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Thibaut, Yann Tang, Nicolas Tran, Hoang Ngoc Vaurijoux, Aurélie Villagrasa, Carmen Incerti, Sébastien Perrot, Yann Nanodosimetric Calculations of Radiation-Induced DNA Damage in a New Nucleus Geometrical Model Based on the Isochore Theory |
title | Nanodosimetric Calculations of Radiation-Induced DNA Damage in a New Nucleus Geometrical Model Based on the Isochore Theory |
title_full | Nanodosimetric Calculations of Radiation-Induced DNA Damage in a New Nucleus Geometrical Model Based on the Isochore Theory |
title_fullStr | Nanodosimetric Calculations of Radiation-Induced DNA Damage in a New Nucleus Geometrical Model Based on the Isochore Theory |
title_full_unstemmed | Nanodosimetric Calculations of Radiation-Induced DNA Damage in a New Nucleus Geometrical Model Based on the Isochore Theory |
title_short | Nanodosimetric Calculations of Radiation-Induced DNA Damage in a New Nucleus Geometrical Model Based on the Isochore Theory |
title_sort | nanodosimetric calculations of radiation-induced dna damage in a new nucleus geometrical model based on the isochore theory |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998209/ https://www.ncbi.nlm.nih.gov/pubmed/35409128 http://dx.doi.org/10.3390/ijms23073770 |
work_keys_str_mv | AT thibautyann nanodosimetriccalculationsofradiationinduceddnadamageinanewnucleusgeometricalmodelbasedontheisochoretheory AT tangnicolas nanodosimetriccalculationsofradiationinduceddnadamageinanewnucleusgeometricalmodelbasedontheisochoretheory AT tranhoangngoc nanodosimetriccalculationsofradiationinduceddnadamageinanewnucleusgeometricalmodelbasedontheisochoretheory AT vaurijouxaurelie nanodosimetriccalculationsofradiationinduceddnadamageinanewnucleusgeometricalmodelbasedontheisochoretheory AT villagrasacarmen nanodosimetriccalculationsofradiationinduceddnadamageinanewnucleusgeometricalmodelbasedontheisochoretheory AT incertisebastien nanodosimetriccalculationsofradiationinduceddnadamageinanewnucleusgeometricalmodelbasedontheisochoretheory AT perrotyann nanodosimetriccalculationsofradiationinduceddnadamageinanewnucleusgeometricalmodelbasedontheisochoretheory |