title: Role of extracellular DNA oxidative modification in radiation induced bystander effects in human endotheliocytes.
abstract: The development of the bystander effect induced by low doses of irradiation in human umbilical vein endothelial cells (HUVECs) depends on extracellular DNA (ecDNA) signaling pathway. We found that the changes in the levels of ROS and NO production by human endothelial cells are components of the radiation induced bystander effect that can be registered at a low dose. We exposed HUVECs to X-ray radiation and studied effects of ecDNA(R) isolated from the culture media conditioned by the short-term incubation of irradiated cells on intact HUVECs. Effects of ecDNA(R) produced by irradiated cells on ROS and NO production in non-irradiated HUVECs are similar to bystander effect. These effects at least partially depend on TLR9 signaling. We compared the production of the nitric oxide and the ROS in human endothelial cells that were (1) irradiated at a low dose; (2) exposed to the ecDNA(R) extracted from the media conditioned by irradiated cells; and (3) exposed to human DNA oxidized in vitro. We found that the cellular responses to all three stimuli described above are essentially similar. We conclude that irradiation-related oxidation of the ecDNA is an important component of the ecDNA-mediated bystander effect.
authors: Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow, Russia.
authors: Svetlana V
authors: SV
authors: Kostyuk
authors: Aleksei V
authors: AV
authors: Ermakov
authors: Anna Yu
authors: AY
authors: Alekseeva
authors: Tatiana D
authors: TD
authors: Smirnova
authors: Kristina V
authors: KV
authors: Glebova
authors: Liudmila V
authors: LV
authors: Efremova
authors: Ancha
authors: A
authors: Baranova
authors: Natalya N
authors: NN
authors: Veiko
mesh_terms: D024201:Bystander Effect / Q000528:radiation effects*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000528:radiation effects*; D006801:Humans; D009569:Nitric Oxide / Q000528:radiation effects; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000528:radiation effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000528:radiation effects; D015398:Signal Transduction; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D014965:X-Rays
chemical_list: D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D009569:Nitric Oxide; D004247:DNA; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III