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Int. J. Mol. Sci. 2017, 18(6), 1176; doi:10.3390/ijms18061176

Dynamic In Vivo Profiling of DNA Damage and Repair after Radiotherapy Using Canine Patients as a Model

1
Division of Radiation Oncology, Vetsuisse Faculty University of Zurich, CH-8057 Zurich, Switzerland
2
Center for Applied Biotechnology and Molecular Medicine (CABMM), University of Zurich, CH-8057 Zurich, Switzerland
3
ZHAW School of Engineering, Zurich University of Applied Sciences, CH-8400 Winterthur, Switzerland
4
Department of Biostatistics, Epidemiology Biostatistics and Prevention Institute, Faculty of Medicine, University of Zurich, CH-8001 Zurich, Switzerland
5
Institute of Veterinary Pathology, Vetsuisse Faculty University of Zurich, CH-8057 Zurich, Switzerland
*
Author to whom correspondence should be addressed.
Academic Editor: Guillermo T. Sáez
Received: 5 April 2017 / Revised: 23 May 2017 / Accepted: 27 May 2017 / Published: 1 June 2017
(This article belongs to the Special Issue DNA Injury and Repair Systems)
View Full-Text   |   Download PDF [3603 KB, uploaded 1 June 2017]   |  

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. View Full-Text
Keywords: DNA damage repair; kinetics; γH2AX-foci; comet assay; dog; radiation; DNA repair model DNA damage repair; kinetics; γH2AX-foci; comet assay; dog; radiation; DNA repair model
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Schulz, N.; Chaachouay, H.; Nytko, K.J.; Weyland, M.S.; Roos, M.; Füchslin, R.M.; Guscetti, F.; Scheidegger, S.; Rohrer Bley, C. Dynamic In Vivo Profiling of DNA Damage and Repair after Radiotherapy Using Canine Patients as a Model. Int. J. Mol. Sci. 2017, 18, 1176.

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