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Dynamic In Vivo profiling of DNA damage and repair after radiotherapy using canine patients as a model


Schulz, Nadine; Chaachouay, Hassan; Nytko, Katarzyna J; Weyland, Mathias S; Roos, Malgorzata; Füchslin, Rudolf M; Guscetti, Franco; Scheidegger, Stephan; Rohrer Bley, Carla (2017). Dynamic In Vivo profiling of DNA damage and repair after radiotherapy using canine patients as a model. International Journal of Molecular Sciences, 18(6):E1176.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Epidemiology, Biostatistics and Prevention Institute (EBPI)
05 Vetsuisse Faculty > Institute of Veterinary Pathology
05 Vetsuisse Faculty > Veterinary Clinic > Department of Small Animals
05 Vetsuisse Faculty > Center for Applied Biotechnology and Molecular Medicine
Dewey Decimal Classification:570 Life sciences; biology
630 Agriculture
Uncontrolled Keywords:DNA damage repair; DNA repair model; comet assay; dog; kinetics; radiation; γH2AX-foci
Language:English
Date:1 June 2017
Deposited On:21 Sep 2017 13:29
Last Modified:21 Sep 2017 16:26
Publisher:MDPI Publishing
ISSN:1422-0067
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.3390/ijms18061176
PubMed ID:28587165

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