Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Oxidative Stress and Deregulated DNA Damage Response Network in Lung Cancer Patients
Δημιουργός/Συγγραφέας:	Stefanou, Dimitra T. Kouvela, Marousa [EL] Στέλλας, Δημήτρης[EN] Stellas, Dimitris [EL] Βουτετάκης, Κωνσταντίνος[EN] Voutetakis, Konstantinos [EL] Παπαδόδημα, Όλγα[EN] Papadodima, Olga Syrigos, Konstantinos [EL] Σουλιώτης, Βασίλης Λ.[EN] Souliotis, Vassilis L.
Ημερομηνία:	2022-05-26
Γλώσσα:	Αγγλικά
ISSN:	2227-9059
DOI:	10.3390/biomedicines10061248
Άλλο:	35740268
Περίληψη:	The deregulated DNA damage response (DDR) network is associated with the onset and progression of cancer. Herein, we searched for DDR defects in peripheral blood mononuclear cells (PBMCs) from lung cancer patients, and we evaluated factors leading to the augmented formation of DNA damage and/or its delayed/decreased removal. In PBMCs from 20 lung cancer patients at diagnosis and 20 healthy controls (HC), we analyzed oxidative stress and DDR-related parameters, including critical DNA repair mechanisms and apoptosis rates. Cancer patients showed higher levels of endogenous DNA damage than HC (p < 0.001), indicating accumulation of DNA damage in the absence of known exogenous genotoxic insults. Higher levels of oxidative stress and apurinic/apyrimidinic sites were observed in patients rather than HC (all p < 0.001), suggesting that increased endogenous DNA damage may emerge, at least in part, from these intracellular factors. Lower nucleotide excision repair and double-strand break repair capacities were found in patients rather than HC (all p < 0.001), suggesting that the accumulation of DNA damage can also be mediated by defective DNA repair mechanisms. Interestingly, reduced apoptosis rates were obtained in cancer patients compared with HC (p < 0.001). Consequently, the expression of critical DDR-associated genes was found deregulated in cancer patients. Together, oxidative stress and DDR-related aberrations contribute to the accumulation of endogenous DNA damage in PBMCs from lung cancer patients and can potentially be exploited as novel therapeutic targets and non-invasive biomarkers.
Τίτλος πηγής δημοσίευσης:	Biomedicines
Τόμος/Κεφάλαιο:	10
Τεύχος:	6
Θεματική Κατηγορία:	[EL] Βιοχημεία[EN] Biochemistry [EL] Νεοπλάσματα. Όγκοι. Ογκολογία (περ. Καρκίνος, κακινογόνες ουσίες)[EN] Neoplasms. Tumors. Oncology (Incl.cancer, carcinogens) [EL] Βιοπληροφορική[EN] Bioinformatics [EL] Γενετική[EN] Genetics [EL] Κυτταρολογία[EN] Cytology
Λέξεις-Κλειδιά:	DNA damage response Apoptosis rates DNA double-strand breaks repair Endogenous DNA damage Lung cancer Nucleotide excision repair Oxidative stress
EU Grant identifier:	8177/10-02-2021
Κάτοχος πνευματικών δικαιωμάτων:	© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Όροι και προϋποθέσεις δικαιωμάτων:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://www.mdpi.com/2227-9059/10/6/1248
Σημειώσεις:	supplementary material at: https://www.mdpi.com/article/10.3390/biomedicines10061248/s1
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο