A Model of Photon Cell Killing Based on the Spatio-Temporal Clustering of DNA Damage in Higher Order Chromatin Structures

We present a new approach to model dose rate effects on cell killing after photon radiation based on the spatio-temporal clustering of DNA double strand breaks (DSBs) within higher order chromatin structures of approximately 1–2 Mbp size, so called giant loops. The main concept of this approach cons...

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Main Authors:	Herr, Lisa, Friedrich, Thomas, Durante, Marco, Scholz, Michael
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879277/

id	pubmed-3879277
recordtype	oai_dc
spelling	pubmed-38792772014-01-03 A Model of Photon Cell Killing Based on the Spatio-Temporal Clustering of DNA Damage in Higher Order Chromatin Structures Herr, Lisa Friedrich, Thomas Durante, Marco Scholz, Michael Research Article We present a new approach to model dose rate effects on cell killing after photon radiation based on the spatio-temporal clustering of DNA double strand breaks (DSBs) within higher order chromatin structures of approximately 1–2 Mbp size, so called giant loops. The main concept of this approach consists of a distinction of two classes of lesions, isolated and clustered DSBs, characterized by the number of double strand breaks induced in a giant loop. We assume a low lethality and fast component of repair for isolated DSBs and a high lethality and slow component of repair for clustered DSBs. With appropriate rates, the temporal transition between the different lesion classes is expressed in terms of five differential equations. These allow formulating the dynamics involved in the competition of damage induction and repair for arbitrary dose rates and fractionation schemes. Final cell survival probabilities are computable with a cell line specific set of three parameters: The lethality for isolated DSBs, the lethality for clustered DSBs and the half-life time of isolated DSBs. Public Library of Science 2014-01-02 /pmc/articles/PMC3879277/ /pubmed/24392100 http://dx.doi.org/10.1371/journal.pone.0083923 Text en © 2014 Herr et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Herr, Lisa Friedrich, Thomas Durante, Marco Scholz, Michael
spellingShingle	Herr, Lisa Friedrich, Thomas Durante, Marco Scholz, Michael A Model of Photon Cell Killing Based on the Spatio-Temporal Clustering of DNA Damage in Higher Order Chromatin Structures
author_facet	Herr, Lisa Friedrich, Thomas Durante, Marco Scholz, Michael
author_sort	Herr, Lisa
title	A Model of Photon Cell Killing Based on the Spatio-Temporal Clustering of DNA Damage in Higher Order Chromatin Structures
title_short	A Model of Photon Cell Killing Based on the Spatio-Temporal Clustering of DNA Damage in Higher Order Chromatin Structures
title_full	A Model of Photon Cell Killing Based on the Spatio-Temporal Clustering of DNA Damage in Higher Order Chromatin Structures
title_fullStr	A Model of Photon Cell Killing Based on the Spatio-Temporal Clustering of DNA Damage in Higher Order Chromatin Structures
title_full_unstemmed	A Model of Photon Cell Killing Based on the Spatio-Temporal Clustering of DNA Damage in Higher Order Chromatin Structures
title_sort	model of photon cell killing based on the spatio-temporal clustering of dna damage in higher order chromatin structures
description	We present a new approach to model dose rate effects on cell killing after photon radiation based on the spatio-temporal clustering of DNA double strand breaks (DSBs) within higher order chromatin structures of approximately 1–2 Mbp size, so called giant loops. The main concept of this approach consists of a distinction of two classes of lesions, isolated and clustered DSBs, characterized by the number of double strand breaks induced in a giant loop. We assume a low lethality and fast component of repair for isolated DSBs and a high lethality and slow component of repair for clustered DSBs. With appropriate rates, the temporal transition between the different lesion classes is expressed in terms of five differential equations. These allow formulating the dynamics involved in the competition of damage induction and repair for arbitrary dose rates and fractionation schemes. Final cell survival probabilities are computable with a cell line specific set of three parameters: The lethality for isolated DSBs, the lethality for clustered DSBs and the half-life time of isolated DSBs.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879277/
_version_	1612043817606709248

A Model of Photon Cell Killing Based on the Spatio-Temporal Clustering of DNA Damage in Higher Order Chromatin Structures

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