TY - JOUR
T1 - Deficient Radiation Transcription Response in COVID-19 Patients
AU - Polozov, Stanislav
AU - Cruz-Garcia, Lourdes
AU - O'Brien, Grainne
AU - Goriacha, Veronika
AU - Nasser, Farah
AU - Jeggo, Penelope
AU - Candéias, Serge
AU - Badie, Christophe
N1 - Publisher Copyright:
© 2023
PY - 2023/7/1
Y1 - 2023/7/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85153598460
U2 - 10.1016/j.adro.2023.101215
DO - 10.1016/j.adro.2023.101215
M3 - Article
AN - SCOPUS:85153598460
SN - 2452-1094
VL - 8
JO - Advances in Radiation Oncology
JF - Advances in Radiation Oncology
IS - 4
M1 - 101215
ER -
