Nanodosimetric simulation of direct ion induced DNA damage using different chromatin geometry modelsCitation formats

  • External authors:
  • Marios Sotiropoulos
  • R. I. Mackay

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Nanodosimetric simulation of direct ion induced DNA damage using different chromatin geometry models. / Henthorn, Nicholas; Warmenhoven, John; Sotiropoulos, Marios; Mackay, R. I.; Kirkby, Karen; Merchant, Michael.

In: Radiation Research, Vol. 188, No. 6, 12.2017, p. 690-703.

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@article{a09d6e1efd7f4e54bd824837d31c72fd,
title = "Nanodosimetric simulation of direct ion induced DNA damage using different chromatin geometry models",
abstract = "Monte 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.",
author = "Nicholas Henthorn and John Warmenhoven and Marios Sotiropoulos and Mackay, {R. I.} and Karen Kirkby and Michael Merchant",
year = "2017",
month = dec,
doi = "10.1667/RR14755.1",
language = "English",
volume = "188",
pages = "690--703",
journal = "Radiation Research",
issn = "0033-7587",
publisher = "Radiation Research Society",
number = "6",

}

RIS

TY - JOUR

T1 - Nanodosimetric simulation of direct ion induced DNA damage using different chromatin geometry models

AU - Henthorn, Nicholas

AU - Warmenhoven, John

AU - Sotiropoulos, Marios

AU - Mackay, R. I.

AU - Kirkby, Karen

AU - Merchant, Michael

PY - 2017/12

Y1 - 2017/12

N2 - Monte 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.

AB - Monte 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.

U2 - 10.1667/RR14755.1

DO - 10.1667/RR14755.1

M3 - Article

VL - 188

SP - 690

EP - 703

JO - Radiation Research

JF - Radiation Research

SN - 0033-7587

IS - 6

ER -