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

Abstract 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...

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Autores principales: Hanns Leonhard Kaatsch, Benjamin Valentin Becker, Simone Schüle, Patrick Ostheim, Kai Nestler, Julia Jakobi, Barbara Schäfer, Thomas Hantke, Marc A. Brockmann, Michael Abend, Stephan Waldeck, Matthias Port, Harry Scherthan, Reinhard Ullmann
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:6b7689fe78db4f4e864aba87add526852021-12-02T17:47:36ZGene expression changes and DNA damage after ex vivo exposure of peripheral blood cells to various CT photon spectra10.1038/s41598-021-91023-72045-2322https://doaj.org/article/6b7689fe78db4f4e864aba87add526852021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91023-7https://doaj.org/toc/2045-2322Abstract 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.Hanns Leonhard KaatschBenjamin Valentin BeckerSimone SchülePatrick OstheimKai NestlerJulia JakobiBarbara SchäferThomas HantkeMarc A. BrockmannMichael AbendStephan WaldeckMatthias PortHarry ScherthanReinhard UllmannNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Hanns Leonhard Kaatsch
Benjamin Valentin Becker
Simone Schüle
Patrick Ostheim
Kai Nestler
Julia Jakobi
Barbara Schäfer
Thomas Hantke
Marc A. Brockmann
Michael Abend
Stephan Waldeck
Matthias Port
Harry Scherthan
Reinhard Ullmann
Gene expression changes and DNA damage after ex vivo exposure of peripheral blood cells to various CT photon spectra
description Abstract 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.
format article
author Hanns Leonhard Kaatsch
Benjamin Valentin Becker
Simone Schüle
Patrick Ostheim
Kai Nestler
Julia Jakobi
Barbara Schäfer
Thomas Hantke
Marc A. Brockmann
Michael Abend
Stephan Waldeck
Matthias Port
Harry Scherthan
Reinhard Ullmann
author_facet Hanns Leonhard Kaatsch
Benjamin Valentin Becker
Simone Schüle
Patrick Ostheim
Kai Nestler
Julia Jakobi
Barbara Schäfer
Thomas Hantke
Marc A. Brockmann
Michael Abend
Stephan Waldeck
Matthias Port
Harry Scherthan
Reinhard Ullmann
author_sort Hanns Leonhard Kaatsch
title 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_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_sort gene expression changes and dna damage after ex vivo exposure of peripheral blood cells to various ct photon spectra
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/6b7689fe78db4f4e864aba87add52685
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