An exposure to the oxidized DNA enhances both instability of genome and survival in cancer cells.
Svetlana V. Kostyuk,Marina S. Konkova,Elizaveta S. Ershova,Anna J. Alekseeva,Tatiana D. Smirnova,Sergey V. Stukalov,Ekaterina A. Kozhina,N. V. Shilova,Tatiana V. Zolotukhina,Zhanna G. Markova,V. L. Izhevskaya,Ancha Baranova,Ancha Baranova,Natalia N. Veiko +13 more
TLDR
It is shown that oxidized extracellular DNA stimulates the survival of MCF-7 tumor cells, and survival of cells with an unstable genome may substantially augment progression of malignancy.Abstract:
Background
Cell free DNA (cfDNA) circulates throughout the bloodstream of both healthy people and patients with various diseases and acts upon the cells. Response to cfDNA depends on concentrations and levels of the damage within cfDNA. Oxidized extracellular DNA acts as a stress signal and elicits an adaptive response.
Principal Findings
Here we show that oxidized extracellular DNA stimulates the survival of MCF-7 tumor cells. Importantly, in cells exposed to oxidized DNA, the suppression of cell death is accompanied by an increase in the markers of genome instability. Short-term exposure to oxidized DNA results in both single- and double strand DNA breaks. Longer treatments evoke a compensatory response that leads to a decrease in the levels of chromatin fragmentations across cell populations. Exposure to oxidized DNA leads to a decrease in the activity of NRF2 and an increase in the activity of NF-kB and STAT3. A model that describes the role of oxidized DNA released from apoptotic cells in tumor biology is proposed.
Conclusions/Significance
Survival of cells with an unstable genome may substantially augment progression of malignancy. Further studies of the effects of extracellular DNA on malignant and normal cells are warranted.read more
Citations
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Vitamin B12 in Relation to Oxidative Stress: A Systematic Review.
Erik E van de Lagemaat,Erik E van de Lagemaat,Lisette C. P. G. M. de Groot,Ellen G. H. M. van den Heuvel +3 more
TL;DR: There is a lack of randomised controlled trials and prospective studies focusing specifically on the relation between B12 and oxidative stress in humans, resulting in a low strength of evidence, and further work is warranted.
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Translocation and deletion breakpoints in cancer genomes are associated with potential non-B DNA-forming sequences.
TL;DR: Analysis of the distribution of PONDS-forming sequences within ±500 bases of 19 947 translocation and 46 365 sequence-characterized deletion breakpoints in cancer genomes finds significant association between PON DS-forming repeats and cancer breakpoints.
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Oxidized extracellular DNA as a stress signal that may modify response to anticancer therapy
K. V. Glebova,Natalya N. Veiko,Svetlana V. Kostyuk,V. L. Izhevskaya,Ancha Baranova,Ancha Baranova +5 more
TL;DR: It seems that tumor cells are more sensitive to oxidized DNA-dependent DNA damage, while developing pronounced adaptive response, which may suggest that in chemotherapy or irradiation-treated human body, the release of oxidizedDNA from dying cancer cells may give a boost to remaining malignant cells by augmenting their survival and stress resistance.
Journal ArticleDOI
Damage-associated molecular patterns in tumor radiotherapy.
TL;DR: The mechanisms behind the release of radiation-induced DAMPs, and its consequences on cells within tumor, are explained to help target these mechanisms in favor of tumor control in combination with radiotherapy and radioimmunotherapy.
Journal ArticleDOI
Quantification of cell-free DNA in blood plasma and DNA damage degree in lymphocytes to evaluate dysregulation of apoptosis in schizophrenia patients.
Elizaveta S. Ershova,E.M. Jestkova,I.V. Chestkov,Lev N. Porokhovnik,Vera Izevskaya,Sergey I. Kutsev,Natalia N. Veiko,Galina Shmarina,Olga A. Dolgikh,S. V. Kostyuk +9 more
TL;DR: Post mortem data indicate a dysregulation of apoptosis in approximately one-third of SZ patients, which leads to an increase in the number of cells with damaged DNA in the patient's body tissues and may be a contributing cause of acute psychotic disorder.
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