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


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
08 06 2021
Historique:
received: 27 10 2020
accepted: 13 05 2021
entrez: 9 6 2021
pubmed: 10 6 2021
medline: 16 11 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 34103547
doi: 10.1038/s41598-021-91023-7
pii: 10.1038/s41598-021-91023-7
pmc: PMC8187728
doi:

Substances chimiques

H2AX protein, human 0
Histones 0
TP53BP1 protein, human 0
Tumor Suppressor p53-Binding Protein 1 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

12060

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Auteurs

Hanns Leonhard Kaatsch (HL)

Bundeswehr Institute of Radiobiology Affiliated to Ulm University, Neuherbergstrasse 11, 80937, Munich, Germany.

Benjamin Valentin Becker (BV)

Department of Radiology, Bundeswehr Central Hospital Koblenz, Rübenacher Straße 170, 56072, Koblenz, Germany. benjamin3becker@bundeswehr.org.

Simone Schüle (S)

Bundeswehr Institute of Radiobiology Affiliated to Ulm University, Neuherbergstrasse 11, 80937, Munich, Germany.

Patrick Ostheim (P)

Bundeswehr Institute of Radiobiology Affiliated to Ulm University, Neuherbergstrasse 11, 80937, Munich, Germany.

Kai Nestler (K)

Department of Radiology, Bundeswehr Central Hospital Koblenz, Rübenacher Straße 170, 56072, Koblenz, Germany.

Julia Jakobi (J)

Bundeswehr Institute of Radiobiology Affiliated to Ulm University, Neuherbergstrasse 11, 80937, Munich, Germany.

Barbara Schäfer (B)

Bundeswehr Institute of Radiobiology Affiliated to Ulm University, Neuherbergstrasse 11, 80937, Munich, Germany.

Thomas Hantke (T)

Bundeswehr Institute of Radiobiology Affiliated to Ulm University, Neuherbergstrasse 11, 80937, Munich, Germany.

Marc A Brockmann (MA)

Department of Neuroradiology, University Medical Center Mainz, Langenbeckstrasse 1, 55101, Mainz, Germany.

Michael Abend (M)

Bundeswehr Institute of Radiobiology Affiliated to Ulm University, Neuherbergstrasse 11, 80937, Munich, Germany.

Stephan Waldeck (S)

Department of Radiology, Bundeswehr Central Hospital Koblenz, Rübenacher Straße 170, 56072, Koblenz, Germany.

Matthias Port (M)

Bundeswehr Institute of Radiobiology Affiliated to Ulm University, Neuherbergstrasse 11, 80937, Munich, Germany.

Harry Scherthan (H)

Bundeswehr Institute of Radiobiology Affiliated to Ulm University, Neuherbergstrasse 11, 80937, Munich, Germany.

Reinhard Ullmann (R)

Bundeswehr Institute of Radiobiology Affiliated to Ulm University, Neuherbergstrasse 11, 80937, Munich, Germany. reinhard1ullmann@bundeswehr.org.

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