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Gene expression changes and DNA damage after ex vivo exposure of peripheral blood cells to various CT photon spectra

Dual-energy CT provides enhanced diagnostic power with similar or even reduced radiation dose as compared to single-energy CT. Its principle is based on the distinct physical properties of low and high energetic photons, which, however, may also affect the biological effectiveness and hence the exte...

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Autores principales: Kaatsch, Hanns Leonhard, Becker, Benjamin Valentin, Schüle, Simone, Ostheim, Patrick, Nestler, Kai, Jakobi, Julia, Schäfer, Barbara, Hantke, Thomas, Brockmann, Marc A., Abend, Michael, Waldeck, Stephan, Port, Matthias, Scherthan, Harry, Ullmann, Reinhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187728/
https://www.ncbi.nlm.nih.gov/pubmed/34103547
http://dx.doi.org/10.1038/s41598-021-91023-7
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author Kaatsch, Hanns Leonhard
Becker, Benjamin Valentin
Schüle, Simone
Ostheim, Patrick
Nestler, Kai
Jakobi, Julia
Schäfer, Barbara
Hantke, Thomas
Brockmann, Marc A.
Abend, Michael
Waldeck, Stephan
Port, Matthias
Scherthan, Harry
Ullmann, Reinhard
author_facet Kaatsch, Hanns Leonhard
Becker, Benjamin Valentin
Schüle, Simone
Ostheim, Patrick
Nestler, Kai
Jakobi, Julia
Schäfer, Barbara
Hantke, Thomas
Brockmann, Marc A.
Abend, Michael
Waldeck, Stephan
Port, Matthias
Scherthan, Harry
Ullmann, Reinhard
author_sort Kaatsch, Hanns Leonhard
collection PubMed
description Dual-energy CT provides enhanced diagnostic power with similar or even reduced radiation dose as compared to single-energy CT. Its principle is based on the distinct physical properties of low and high energetic photons, which, however, may also affect the biological effectiveness and hence the extent of CT-induced cellular damage. Therefore, a comparative analysis of biological effectiveness of dual- and single-energy CT scans with focus on early gene regulation and frequency of radiation-induced DNA double strand breaks (DSBs) was performed. Blood samples from three healthy individuals were irradiated ex vivo with single-energy (80 kV and 150 kV) and dual-energy tube voltages (80 kV/Sn150kV) employing a modern dual source CT scanner resulting in Volume Computed Tomography Dose Index (CTDIvol) of 15.79–18.26 mGy and dose length product (DLP) of 606.7–613.8 mGy*cm. Non-irradiated samples served as a control. Differential gene expression in peripheral blood mononuclear cells was analyzed 6 h after irradiation using whole transcriptome sequencing. DSB frequency was studied by 53BP1 + γH2AX co-immunostaining and microscopic evaluation of their focal accumulation at DSBs. Neither the analysis of gene expression nor DSB frequency provided any evidence for significantly increased biological effectiveness of dual-energy CT in comparison to samples irradiated with particular single-energy CT spectra. Relative to control, irradiated samples were characterized by a significantly higher rate of DSBs (p < 0.001) and the shared upregulation of five genes, AEN, BAX, DDB2, FDXR and EDA2R, which have already been suggested as radiation-induced biomarkers in previous studies. Despite steadily decreasing doses, CT diagnostics remain a genotoxic stressor with impact on gene regulation and DNA integrity. However, no evidence was found that varying X-ray spectra of CT impact the extent of cellular damage.
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spelling pubmed-81877282021-06-10 Gene expression changes and DNA damage after ex vivo exposure of peripheral blood cells to various CT photon spectra Kaatsch, Hanns Leonhard Becker, Benjamin Valentin Schüle, Simone Ostheim, Patrick Nestler, Kai Jakobi, Julia Schäfer, Barbara Hantke, Thomas Brockmann, Marc A. Abend, Michael Waldeck, Stephan Port, Matthias Scherthan, Harry Ullmann, Reinhard Sci Rep Article Dual-energy CT provides enhanced diagnostic power with similar or even reduced radiation dose as compared to single-energy CT. Its principle is based on the distinct physical properties of low and high energetic photons, which, however, may also affect the biological effectiveness and hence the extent of CT-induced cellular damage. Therefore, a comparative analysis of biological effectiveness of dual- and single-energy CT scans with focus on early gene regulation and frequency of radiation-induced DNA double strand breaks (DSBs) was performed. Blood samples from three healthy individuals were irradiated ex vivo with single-energy (80 kV and 150 kV) and dual-energy tube voltages (80 kV/Sn150kV) employing a modern dual source CT scanner resulting in Volume Computed Tomography Dose Index (CTDIvol) of 15.79–18.26 mGy and dose length product (DLP) of 606.7–613.8 mGy*cm. Non-irradiated samples served as a control. Differential gene expression in peripheral blood mononuclear cells was analyzed 6 h after irradiation using whole transcriptome sequencing. DSB frequency was studied by 53BP1 + γH2AX co-immunostaining and microscopic evaluation of their focal accumulation at DSBs. Neither the analysis of gene expression nor DSB frequency provided any evidence for significantly increased biological effectiveness of dual-energy CT in comparison to samples irradiated with particular single-energy CT spectra. Relative to control, irradiated samples were characterized by a significantly higher rate of DSBs (p < 0.001) and the shared upregulation of five genes, AEN, BAX, DDB2, FDXR and EDA2R, which have already been suggested as radiation-induced biomarkers in previous studies. Despite steadily decreasing doses, CT diagnostics remain a genotoxic stressor with impact on gene regulation and DNA integrity. However, no evidence was found that varying X-ray spectra of CT impact the extent of cellular damage. Nature Publishing Group UK 2021-06-08 /pmc/articles/PMC8187728/ /pubmed/34103547 http://dx.doi.org/10.1038/s41598-021-91023-7 Text en © The Author(s) 2021, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kaatsch, Hanns Leonhard
Becker, Benjamin Valentin
Schüle, Simone
Ostheim, Patrick
Nestler, Kai
Jakobi, Julia
Schäfer, Barbara
Hantke, Thomas
Brockmann, Marc A.
Abend, Michael
Waldeck, Stephan
Port, Matthias
Scherthan, Harry
Ullmann, Reinhard
Gene expression changes and DNA damage after ex vivo exposure of peripheral blood cells to various CT photon spectra
title Gene expression changes and DNA damage after ex vivo exposure of peripheral blood cells to various CT photon spectra
title_full Gene expression changes and DNA damage after ex vivo exposure of peripheral blood cells to various CT photon spectra
title_fullStr Gene expression changes and DNA damage after ex vivo exposure of peripheral blood cells to various CT photon spectra
title_full_unstemmed Gene expression changes and DNA damage after ex vivo exposure of peripheral blood cells to various CT photon spectra
title_short Gene expression changes and DNA damage after ex vivo exposure of peripheral blood cells to various CT photon spectra
title_sort gene expression changes and dna damage after ex vivo exposure of peripheral blood cells to various ct photon spectra
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187728/
https://www.ncbi.nlm.nih.gov/pubmed/34103547
http://dx.doi.org/10.1038/s41598-021-91023-7
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