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Persistent DNA Double-Strand Breaks After Repeated Diagnostic CT Scans in Breast Epithelial Cells and Lymphocytes

DNA double-strand break (DSB) induction and repair have been widely studied in radiation therapy (RT); however little is known about the impact of very low exposures from repeated computed tomography (CT) scans for the efficiency of repair. In our current study, DSB repair and kinetics were investig...

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Autores principales: Bogdanova, Natalia V., Jguburia, Nina, Ramachandran, Dhanya, Nischik, Nora, Stemwedel, Katharina, Stamm, Georg, Werncke, Thomas, Wacker, Frank, Dörk, Thilo, Christiansen, Hans
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103218/
https://www.ncbi.nlm.nih.gov/pubmed/33968734
http://dx.doi.org/10.3389/fonc.2021.634389
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author Bogdanova, Natalia V.
Jguburia, Nina
Ramachandran, Dhanya
Nischik, Nora
Stemwedel, Katharina
Stamm, Georg
Werncke, Thomas
Wacker, Frank
Dörk, Thilo
Christiansen, Hans
author_facet Bogdanova, Natalia V.
Jguburia, Nina
Ramachandran, Dhanya
Nischik, Nora
Stemwedel, Katharina
Stamm, Georg
Werncke, Thomas
Wacker, Frank
Dörk, Thilo
Christiansen, Hans
author_sort Bogdanova, Natalia V.
collection PubMed
description DNA double-strand break (DSB) induction and repair have been widely studied in radiation therapy (RT); however little is known about the impact of very low exposures from repeated computed tomography (CT) scans for the efficiency of repair. In our current study, DSB repair and kinetics were investigated in side-by-side comparison of RT treatment (2 Gy) with repeated diagnostic CT scans (≤20 mGy) in human breast epithelial cell lines and lymphoblastoid cells harboring different mutations in known DNA damage repair proteins. Immunocytochemical analysis of well known DSB markers γH2AX and 53BP1, within 48 h after each treatment, revealed highly correlated numbers of foci and similar appearance/disappearance profiles. The levels of γH2AX and 53BP1 foci after CT scans were up to 30% of those occurring 0.5 h after 2 Gy irradiation. The DNA damage repair after diagnostic CT scans was monitored and quantitatively assessed by both γH2AX and 53BP1 foci in different cell types. Subsequent diagnostic CT scans in 6 and/or 12 weeks intervals resulted in elevated background levels of repair foci, more pronounced in cells that were prone to genomic instability due to mutations in known regulators of DNA damage response (DDR). The levels of persistent foci remained enhanced for up to 6 months. This “memory effect” may reflect a radiation-induced long-term response of cells after low-dose x-ray exposure.
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spelling pubmed-81032182021-05-08 Persistent DNA Double-Strand Breaks After Repeated Diagnostic CT Scans in Breast Epithelial Cells and Lymphocytes Bogdanova, Natalia V. Jguburia, Nina Ramachandran, Dhanya Nischik, Nora Stemwedel, Katharina Stamm, Georg Werncke, Thomas Wacker, Frank Dörk, Thilo Christiansen, Hans Front Oncol Oncology DNA double-strand break (DSB) induction and repair have been widely studied in radiation therapy (RT); however little is known about the impact of very low exposures from repeated computed tomography (CT) scans for the efficiency of repair. In our current study, DSB repair and kinetics were investigated in side-by-side comparison of RT treatment (2 Gy) with repeated diagnostic CT scans (≤20 mGy) in human breast epithelial cell lines and lymphoblastoid cells harboring different mutations in known DNA damage repair proteins. Immunocytochemical analysis of well known DSB markers γH2AX and 53BP1, within 48 h after each treatment, revealed highly correlated numbers of foci and similar appearance/disappearance profiles. The levels of γH2AX and 53BP1 foci after CT scans were up to 30% of those occurring 0.5 h after 2 Gy irradiation. The DNA damage repair after diagnostic CT scans was monitored and quantitatively assessed by both γH2AX and 53BP1 foci in different cell types. Subsequent diagnostic CT scans in 6 and/or 12 weeks intervals resulted in elevated background levels of repair foci, more pronounced in cells that were prone to genomic instability due to mutations in known regulators of DNA damage response (DDR). The levels of persistent foci remained enhanced for up to 6 months. This “memory effect” may reflect a radiation-induced long-term response of cells after low-dose x-ray exposure. Frontiers Media S.A. 2021-04-23 /pmc/articles/PMC8103218/ /pubmed/33968734 http://dx.doi.org/10.3389/fonc.2021.634389 Text en Copyright © 2021 Bogdanova, Jguburia, Ramachandran, Nischik, Stemwedel, Stamm, Werncke, Wacker, Dörk and Christiansen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Bogdanova, Natalia V.
Jguburia, Nina
Ramachandran, Dhanya
Nischik, Nora
Stemwedel, Katharina
Stamm, Georg
Werncke, Thomas
Wacker, Frank
Dörk, Thilo
Christiansen, Hans
Persistent DNA Double-Strand Breaks After Repeated Diagnostic CT Scans in Breast Epithelial Cells and Lymphocytes
title Persistent DNA Double-Strand Breaks After Repeated Diagnostic CT Scans in Breast Epithelial Cells and Lymphocytes
title_full Persistent DNA Double-Strand Breaks After Repeated Diagnostic CT Scans in Breast Epithelial Cells and Lymphocytes
title_fullStr Persistent DNA Double-Strand Breaks After Repeated Diagnostic CT Scans in Breast Epithelial Cells and Lymphocytes
title_full_unstemmed Persistent DNA Double-Strand Breaks After Repeated Diagnostic CT Scans in Breast Epithelial Cells and Lymphocytes
title_short Persistent DNA Double-Strand Breaks After Repeated Diagnostic CT Scans in Breast Epithelial Cells and Lymphocytes
title_sort persistent dna double-strand breaks after repeated diagnostic ct scans in breast epithelial cells and lymphocytes
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103218/
https://www.ncbi.nlm.nih.gov/pubmed/33968734
http://dx.doi.org/10.3389/fonc.2021.634389
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