title: Oxidized extracellular DNA as a stress signal in human cells.
abstract: The term "cell-free DNA" (cfDNA) was recently coined for DNA fragments from plasma/serum, while DNA present in in vitro cell culture media is known as extracellular DNA (ecDNA). Under oxidative stress conditions, the levels of oxidative modification of cellular DNA and the rate of cell death increase. Dying cells release their damaged DNA, thus, contributing oxidized DNA fragments to the pool of cfDNA/ecDNA. Oxidized cell-free DNA could serve as a stress signal that promotes irradiation-induced bystander effect. Evidence points to TLR9 as a possible candidate for oxidized DNA sensor. An exposure to oxidized ecDNA stimulates a synthesis of reactive oxygen species (ROS) that evokes an adaptive response that includes transposition of the homologous loci within the nucleus, polymerization and the formation of the stress fibers of the actin, as well as activation of the ribosomal gene expression, and nuclear translocation of NF-E2 related factor-2 (NRF2) that, in turn, mediates induction of phase II detoxifying and antioxidant enzymes. In conclusion, the oxidized DNA is a stress signal released in response to oxidative stress in the cultured cells and, possibly, in the human body; in particular, it might contribute to systemic abscopal effects of localized irradiation treatments.
authors.affiliation: Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Mosskvorechie street 1, Moscow 115478, Russia.
authors.forename: Aleksei V
authors.initials: AV
authors.lastname: Ermakov
authors.forename: Marina S
authors.initials: MS
authors.lastname: Konkova
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Kostyuk
authors.forename: Vera L
authors.initials: VL
authors.lastname: Izevskaya
authors.forename: Ancha
authors.initials: A
authors.lastname: Baranova
authors.forename: Natalya N
authors.initials: NN
authors.lastname: Veiko
mesh_terms: D000818:Animals; D017209:Apoptosis; D004247:DNA / Q000097:blood / Q000737:chemistry*; D004249:DNA Damage; D015894:Genome, Human; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D004247:DNA