Oxidative stress as a significant factor for development of an adaptive response in irradiated and nonirradiated human lymphocytes after inducing the bystander effect by low-dose X-radiation.
X-radiation (10cGy) was shown to induce in human lymphocytes transposition of homologous chromosomes loci from the membrane towards the centre of the nucleus and activation of the chromosomal nucleolus-forming regions (NFRs). These effects are transmitted by means of extracellular DNA (ecDNA) fragments to nonirradiated cells (the so-called bystander effect, BE). We demonstrated that in the development of the BE an important role is played by oxidative stress (which is brought about by low radiation doses and ecDNA fragments of the culture medium of the irradiated cells), by an enzyme of apoptosis called caspase-3, and by DNA-binding receptors of the bystander cells, presumably TLR9. Proposed herein is a scheme of the development of an adaptive response and the BE on exposure to radiation. Ionizing radiation induces apoptosis of the radiosensitive fraction of cells due to the development of the "primary" oxidative stress (OS). DNA fragments of apoptotic cells are released into the intercellular space and interact with the DNA-binding receptors of the bystander cells. This interaction activates in lymphocytes signalling pathways associated with synthesis of the reactive oxygen species and nitrogen species, i.e., induces secondary oxidative stress accompanied by apoptosis of part of the cells, etc. Hence, single exposure to radiation may be followed by relatively long-lasting in the cellular population oxidative stress contributing to the development of an adaptive response. We thus believe that ecDNA of irradiated apoptotic lymphocytes is a significant factor of stress-signalling.
Ermakov
Aleksei V
AV
Research Centre for Medical Genetics, Russian Academy of Medical Science, Moscow, Russia. avePlato@mail.ru
Konkova
Marina S
MS
Kostyuk
Svetlana V
SV
Egolina
Natalya A
NA
Efremova
Liudmila V
LV
Veiko
Natalya N
NN
D017209:Apoptosis / Q000528:radiation effects*; D024201:Bystander Effect / Q000528:radiation effects*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000528:radiation effects*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D014965:X-Rays
D016877:Oxidants; D017382:Reactive Oxygen Species; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D004247:DNA; D006861:Hydrogen Peroxide; D053148:Caspase 3