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Title: Dynamic in vivo profiling of DNA damage and repair after radiotherapy using canine patients as a model
Authors : Schulz, Nadine
Chaachouay, Hassan
Nytko, Katarzyna J.
Weyland, Mathias S.
Roos, Malgorzata
Füchslin, Rudolf Marcel
Guscetti, Franco
Scheidegger, Stephan
Rohrer Bley, Carla
Published in : International Journal of Molecular Sciences
Volume(Issue) : 18
Issue : 6/1176
Publisher / Ed. Institution : MDPI AG
Issue Date: 2017
License (according to publishing contract) : CC BY 4.0: Namensnennung 4.0 International
Type of review: Peer review (Publication)
Language : English
Subjects : Comet assay; Repair kinetics; Repair pathway model
Subject (DDC) : 572: Biochemistry
Abstract: Time resolved data of DNA damage and repair after radiotherapy elucidates the relation between damage, repair, and cell survival. While well characterized in vitro, little is known about the time-course of DNA damage response in tumors sampled from individual patients. Kinetics of DNA damage after radiotherapy was assessed in eight dogs using repeated in vivo samples of tumor and co-irradiated normal tissue analyzed with comet assay and phosphorylated H2AX (γH2AX) immunohistochemistry. In vivo results were then compared (in silico) with a dynamic mathematical model for DNA damage formation and repair. Maximum %DNA in tail was observed at 15–60 min after irradiation, with a rapid decrease. Time-courses of γH2AX-foci paralleled these findings with a small time delay and were not influenced by covariates. The evolutionary parameter search based on %DNA in tail revealed a good fit of the DNA repair model to in vivo data for pooled sarcoma time-courses, but fits for individual sarcoma time-courses suffer from the heterogeneous nature of the in vivo data. It was possible to follow dynamics of comet tail intensity and γH2AX-foci during a course of radiation using a minimally invasive approach. DNA repair can be quantitatively investigated as time-courses of individual patients by integrating this resulting data into a dynamic mathematical model.
Departement: School of Engineering
Organisational Unit: Institute of Applied Mathematics and Physics (IAMP)
Publication type: Article in scientific Journal
DOI : 10.3390/ijms18061176
ISSN: 1422-0067
Appears in Collections:Publikationen School of Engineering

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