Cargando…
Heterogeneity of γH2AX Foci Increases in Ex Vivo Biopsies Relative to In Vivo Tumors
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 sta...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163410/ https://www.ncbi.nlm.nih.gov/pubmed/30181446 http://dx.doi.org/10.3390/ijms19092616 |
_version_ | 1783359354393591808 |
---|---|
author | Rassamegevanon, Treewut Löck, Steffen Baumann, Michael Krause, Mechthild von Neubeck, Cläre |
author_facet | Rassamegevanon, Treewut Löck, Steffen Baumann, Michael Krause, Mechthild von Neubeck, Cläre |
author_sort | Rassamegevanon, Treewut |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6163410 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-61634102018-10-10 Heterogeneity of γH2AX Foci Increases in Ex Vivo Biopsies Relative to In Vivo Tumors Rassamegevanon, Treewut Löck, Steffen Baumann, Michael Krause, Mechthild von Neubeck, Cläre Int J Mol Sci Article 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. MDPI 2018-09-04 /pmc/articles/PMC6163410/ /pubmed/30181446 http://dx.doi.org/10.3390/ijms19092616 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rassamegevanon, Treewut Löck, Steffen Baumann, Michael Krause, Mechthild von Neubeck, Cläre Heterogeneity of γH2AX Foci Increases in Ex Vivo Biopsies Relative to In Vivo Tumors |
title | Heterogeneity of γH2AX Foci Increases in Ex Vivo Biopsies Relative to In Vivo Tumors |
title_full | Heterogeneity of γH2AX Foci Increases in Ex Vivo Biopsies Relative to In Vivo Tumors |
title_fullStr | Heterogeneity of γH2AX Foci Increases in Ex Vivo Biopsies Relative to In Vivo Tumors |
title_full_unstemmed | Heterogeneity of γH2AX Foci Increases in Ex Vivo Biopsies Relative to In Vivo Tumors |
title_short | Heterogeneity of γH2AX Foci Increases in Ex Vivo Biopsies Relative to In Vivo Tumors |
title_sort | heterogeneity of γh2ax foci increases in ex vivo biopsies relative to in vivo tumors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163410/ https://www.ncbi.nlm.nih.gov/pubmed/30181446 http://dx.doi.org/10.3390/ijms19092616 |
work_keys_str_mv | AT rassamegevanontreewut heterogeneityofgh2axfociincreasesinexvivobiopsiesrelativetoinvivotumors AT locksteffen heterogeneityofgh2axfociincreasesinexvivobiopsiesrelativetoinvivotumors AT baumannmichael heterogeneityofgh2axfociincreasesinexvivobiopsiesrelativetoinvivotumors AT krausemechthild heterogeneityofgh2axfociincreasesinexvivobiopsiesrelativetoinvivotumors AT vonneubeckclare heterogeneityofgh2axfociincreasesinexvivobiopsiesrelativetoinvivotumors |