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Int. J. Mol. Sci. 2018, 19(9), 2616; https://doi.org/10.3390/ijms19092616

Heterogeneity of γH2AX Foci Increases in Ex Vivo Biopsies Relative to In Vivo Tumors

1,2
,
1,2,3,4
,
1,2,3,4,5,6,7,8,9
,
1,2,3,4,5,6,7,8
and
1,2,4,*
1
OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
2
OncoRay-National Center for Radiation Research in Oncology, Helmholtz-Zentrum Dresden-Rossendorf, 01328 Dresden, Germany
3
Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
4
German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
5
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology-OncoRay, 01328 Dresden, Germany
6
National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
7
National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
8
National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany
9
German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Received: 3 July 2018 / Revised: 13 August 2018 / Accepted: 16 August 2018 / Published: 4 September 2018
(This article belongs to the Special Issue Advances and Challenges in Biomolecular Radiation Research)
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Abstract

The biomarker for DNA double stand breaks, gammaH2AX (γH2AX), holds a high potential as an intrinsic radiosensitivity predictor of tumors in clinical practice. Here, two published γH2AX foci datasets from in and ex vivo exposed human head and neck squamous cell carcinoma (hHNSCC) xenografts were statistically re-evaluated for the effect of the assay setting (in or ex vivo) on cellular geometry and the degree of heterogeneity in γH2AX foci. Significant differences between the nucleus areas of in- and ex vivo exposed samples were found. However, the number of foci increased linearly with nucleus area in irradiated samples of both settings. Moreover, irradiated tumor cells showed changes of nucleus area distributions towards larger areas compared to unexposed samples, implying cell cycle alteration after radiation exposure. The number of residual γH2AX foci showed a higher degree of intra-tumoral heterogeneity in the ex vivo exposed samples relative to the in vivo exposed samples. In the in vivo setting, the highest intra-tumoral heterogeneity was observed in initial γH2AX foci numbers (foci detected 30 min following irradiation). These results suggest that the tumor microenvironment and the culture condition considerably influence cellular adaptation and DNA damage repair. View Full-Text
Keywords: radiation; predictive biomarker; DNA damage response; mixed model statistics radiation; predictive biomarker; DNA damage response; mixed model statistics
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Rassamegevanon, T.; Löck, S.; Baumann, M.; Krause, M.; von Neubeck, C. Heterogeneity of γH2AX Foci Increases in Ex Vivo Biopsies Relative to In Vivo Tumors. Int. J. Mol. Sci. 2018, 19, 2616.

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