Deficient Radiation Transcription Response in COVID-19 Patients.

Autor:	Polozov S; Science Limited, St. Ives, Cambridgeshire, United Kingdom., Cruz-Garcia L; Cancer Mechanisms and Biomarkers Group, Radiation Effects Department, Radiation, Chemical & Environmental Hazards, Harwell Campus, UK Health Security Agency, Didcot, Oxfordshire, United Kingdom., O'Brien G; Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, United Kingdom., Goriacha V; Science Limited, St. Ives, Cambridgeshire, United Kingdom., Nasser F; Cancer Mechanisms and Biomarkers Group, Radiation Effects Department, Radiation, Chemical & Environmental Hazards, Harwell Campus, UK Health Security Agency, Didcot, Oxfordshire, United Kingdom., Jeggo P; Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, United Kingdom., Candéias S; Commissariat à l'Energie Atomique et aux Energies Renouvelables, Centre National de la Recherche Scientifique, Interdisciplinary Research Institute - Grenoble, Laboratory of Chemistry and Biology of Metals, Unité mixte de Recherche 5249, 38054, Grenoble, France., Badie C; Cancer Mechanisms and Biomarkers Group, Radiation Effects Department, Radiation, Chemical & Environmental Hazards, Harwell Campus, UK Health Security Agency, Didcot, Oxfordshire, United Kingdom.
Jazyk:	angličtina
Zdroj:	Advances in radiation oncology [Adv Radiat Oncol] 2023 Mar 25; Vol. 8 (4), pp. 101215. Date of Electronic Publication: 2023 Mar 25 (Print Publication: 2023).
DOI:	10.1016/j.adro.2023.101215
Abstrakt:	Purpose: The ongoing SARS-CoV-2 pandemic has resulted in over 6.3 million deaths and 560 million COVID-19 cases worldwide. Clinical management of hospitalized patients is complex due to the heterogeneous course of COVID-19. Low-dose radiation therapy is known to dampen localized chronic inflammation and has been suggested to be used to reduce lung inflammation in patients with COVID-19. However, it is unknown whether SARS-CoV-2 alters the radiation response and associated radiation exposure related risk. Methods and Materials: We generated gene expression profiles from circulating leukocytes of hospitalized patients with COVID-19 and healthy donors. Results: The p53 signaling pathway was found to be dysregulated, with mRNA levels of p53, ATM , and CHK2 being lower in patients with COVID-19. Several key p53 target genes involved in cell cycle arrest, apoptosis, and p53 feedback inhibition were upregulated in patients with COVID-19 while other p53 target genes were downregulated. This dysregulation has functional consequences as the transcription of p53 -dependant genes ( CCNG1, GADD45A, DDB2, SESN1, FDXR, APOBEC ) was reduced 24 hours after x-ray exposure ex vivo to both low (100 mGy) or high (2 Gy) doses. Conclusions: SARS-CoV-2 infection affects a DNA damage response that may modify radiation-induced health risks in exposed patients with COVID-19. (Crown Copyright © 2023 Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.)
Databáze:	MEDLINE
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