Oxidative Stress and Deregulated DNA Damage Response Network in Lung Cancer Patients
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/6/1248 |
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| author | Dimitra T. Stefanou Marousa Kouvela Dimitris Stellas Konstantinos Voutetakis Olga Papadodima Konstantinos Syrigos Vassilis L. Souliotis |
| author_facet | Dimitra T. Stefanou Marousa Kouvela Dimitris Stellas Konstantinos Voutetakis Olga Papadodima Konstantinos Syrigos Vassilis L. Souliotis |
| author_sort | Dimitra T. Stefanou |
| collection | DOAJ |
| description | 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 (<i>p</i> < 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 <i>p</i> < 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 <i>p</i> < 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 (<i>p</i> < 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. |
| first_indexed | 2024-03-10T00:21:48Z |
| format | Article |
| id | doaj.art-6872aaa444a04896bb07cef347dc0832 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T00:21:48Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-6872aaa444a04896bb07cef347dc08322023-11-23T15:41:28ZengMDPI AGBiomedicines2227-90592022-05-01106124810.3390/biomedicines10061248Oxidative Stress and Deregulated DNA Damage Response Network in Lung Cancer PatientsDimitra T. Stefanou0Marousa Kouvela1Dimitris Stellas2Konstantinos Voutetakis3Olga Papadodima4Konstantinos Syrigos5Vassilis L. Souliotis6First Department of Medicine, Laiko General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, GreeceOncology Unit, Third Department of Medicine, Sotiria General Hospital, School of Medicine, University of Athens, 11527 Athens, GreeceInstitute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, GreeceInstitute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, GreeceInstitute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, GreeceOncology Unit, Third Department of Medicine, Sotiria General Hospital, School of Medicine, University of Athens, 11527 Athens, GreeceInstitute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, GreeceThe 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 (<i>p</i> < 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 <i>p</i> < 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 <i>p</i> < 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 (<i>p</i> < 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.https://www.mdpi.com/2227-9059/10/6/1248lung cancerDNA damage responseoxidative stressendogenous DNA damagenucleotide excision repairdouble-strand breaks repair |
| spellingShingle | Dimitra T. Stefanou Marousa Kouvela Dimitris Stellas Konstantinos Voutetakis Olga Papadodima Konstantinos Syrigos Vassilis L. Souliotis Oxidative Stress and Deregulated DNA Damage Response Network in Lung Cancer Patients Biomedicines lung cancer DNA damage response oxidative stress endogenous DNA damage nucleotide excision repair double-strand breaks repair |
| title | Oxidative Stress and Deregulated DNA Damage Response Network in Lung Cancer Patients |
| title_full | Oxidative Stress and Deregulated DNA Damage Response Network in Lung Cancer Patients |
| title_fullStr | Oxidative Stress and Deregulated DNA Damage Response Network in Lung Cancer Patients |
| title_full_unstemmed | Oxidative Stress and Deregulated DNA Damage Response Network in Lung Cancer Patients |
| title_short | Oxidative Stress and Deregulated DNA Damage Response Network in Lung Cancer Patients |
| title_sort | oxidative stress and deregulated dna damage response network in lung cancer patients |
| topic | lung cancer DNA damage response oxidative stress endogenous DNA damage nucleotide excision repair double-strand breaks repair |
| url | https://www.mdpi.com/2227-9059/10/6/1248 |
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