title: An exposure to the oxidized DNA enhances both instability of genome and survival in cancer cells.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow, Russia.
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Kostyuk
authors.forename: Marina S
authors.initials: MS
authors.lastname: Konkova
authors.forename: Elizaveta S
authors.initials: ES
authors.lastname: Ershova
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Alekseeva
authors.forename: Tatiana D
authors.initials: TD
authors.lastname: Smirnova
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Stukalov
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Kozhina
authors.forename: Nadezda V
authors.initials: NV
authors.lastname: Shilova
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Zolotukhina
authors.forename: Zhanna G
authors.initials: ZG
authors.lastname: Markova
authors.forename: Vera L
authors.initials: VL
authors.lastname: Izhevskaya
authors.forename: Ancha
authors.initials: A
authors.lastname: Baranova
authors.forename: Natalia N
authors.initials: NN
authors.lastname: Veiko
mesh_terms: D001692:Biological Transport; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002470:Cell Survival; D053960:DNA Breaks; D004249:DNA Damage; D004270:DNA, Circular / Q000378:metabolism*; D004268:DNA-Binding Proteins; D042822:Genomic Instability; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D061986:MCF-7 Cells; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism
chemical_list: C410167:AIM2 protein, human; D004270:DNA, Circular; D004268:DNA-Binding Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; D051217:Toll-Like Receptor 9