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dc.contributor.authorHenthorn, N
dc.contributor.authorWarmenhoven, J
dc.contributor.authorSotiropoulos, M
dc.contributor.authorMackay, Ranald I
dc.contributor.authorKirkby, Karen J
dc.contributor.authorMerchant, Michael J
dc.date.accessioned2017-09-08T11:31:45Z
dc.date.available2017-09-08T11:31:45Z
dc.date.issued2017-08-09
dc.identifier.citationNanodosimetric simulation of direct ion-induced DNA damage using different chromatin geometry models. 2017 Radiat Resen
dc.identifier.issn1938-5404
dc.identifier.pmid28792846
dc.identifier.doi10.1667/RR14755.1
dc.identifier.urihttp://hdl.handle.net/10541/620548
dc.description.abstractMonte Carlo based simulation has proven useful in investigating the effect of proton-induced DNA damage and the processes through which this damage occurs. Clustering of ionizations within a small volume can be related to DNA damage through the principles of nanodosimetry. For simulation, it is standard to construct a small volume of water and determine spatial clusters. More recently, realistic DNA geometries have been used, tracking energy depositions within DNA backbone volumes. Traditionally a chromatin fiber is built within the simulation and identically replicated throughout a cell nucleus, representing the cell in interphase. However, the in vivo geometry of the chromatin fiber is still unknown within the literature, with many proposed models. In this work, the Geant4-DNA toolkit was used to build three chromatin models: the solenoid, zig-zag and cross-linked geometries. All fibers were built to the same chromatin density of 4.2 nucleosomes/11 nm. The fibers were then LET proton irradiated (5-80 keV/μm) or LET alpha-particle irradiated (63-226 keV/μm). Nanodosimetric parameters were scored for each fiber after each LET and used as a comparator among the models. Statistically significant differences were observed in the double-strand break backbone size distributions among the models, although nonsignificant differences were noted among the nanodosimetric parameters. From the data presented in this article, we conclude that selection of the solenoid, zig-zag or cross-linked chromatin model does not significantly affect the calculated nanodosimetric parameters. This allows for a simulation-based cell model to make use of any of these chromatin models for the scoring of direct ion-induced DNA damage.
dc.language.isoenen
dc.rightsArchived with thanks to Radiation researchen
dc.titleNanodosimetric Simulation of Direct Ion-Induced DNANanodosimetric simulation of direct ion-induced DNA damage using different chromatin geometry models.en
dc.typeArticleen
dc.contributor.departmentDivision of Molecular and Clinical Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, United Kingdomen
dc.identifier.journalRadiation Researchen
html.description.abstractMonte Carlo based simulation has proven useful in investigating the effect of proton-induced DNA damage and the processes through which this damage occurs. Clustering of ionizations within a small volume can be related to DNA damage through the principles of nanodosimetry. For simulation, it is standard to construct a small volume of water and determine spatial clusters. More recently, realistic DNA geometries have been used, tracking energy depositions within DNA backbone volumes. Traditionally a chromatin fiber is built within the simulation and identically replicated throughout a cell nucleus, representing the cell in interphase. However, the in vivo geometry of the chromatin fiber is still unknown within the literature, with many proposed models. In this work, the Geant4-DNA toolkit was used to build three chromatin models: the solenoid, zig-zag and cross-linked geometries. All fibers were built to the same chromatin density of 4.2 nucleosomes/11 nm. The fibers were then LET proton irradiated (5-80 keV/μm) or LET alpha-particle irradiated (63-226 keV/μm). Nanodosimetric parameters were scored for each fiber after each LET and used as a comparator among the models. Statistically significant differences were observed in the double-strand break backbone size distributions among the models, although nonsignificant differences were noted among the nanodosimetric parameters. From the data presented in this article, we conclude that selection of the solenoid, zig-zag or cross-linked chromatin model does not significantly affect the calculated nanodosimetric parameters. This allows for a simulation-based cell model to make use of any of these chromatin models for the scoring of direct ion-induced DNA damage.


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