TY - JOUR

T1 - Characterization of biological peculiarities of the radioprotective activity of double-stranded RNA isolated from Saccharomyces сerevisiae

AU - Ritter, Genrikh S.

AU - Nikolin, Valeriy P.

AU - Popova, Nelly A.

AU - Proskurina, Anastasia S.

AU - Kisaretova, Polina E.

AU - Taranov, Oleg S.

AU - Dubatolova, Tatiana D.

AU - Dolgova, Evgenia V.

AU - Potter, Ekaterina A.

AU - Kirikovich, Svetlana S.

AU - Efremov, Yaroslav R.

AU - Bayborodin, Sergey I.

AU - Romanenko, Margarita V.

AU - Meschaninova, Maria I.

AU - Venyaminova, Aliya G.

AU - Kolchanov, Nikolay A.

AU - Shurdov, Mikhail A.

AU - Bogachev, Sergey S.

N1 - Publisher Copyright: © Copyright © 2020 Taylor & Francis Group LLC. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/9/1

Y1 - 2020/9/1

N2 - The purpose of the article: Protection from ionizing radiation is the most important component in the curing malignant neoplasms, servicing atomic reactors, and resolving the situations associated with uncontrolled radioactive pollutions. In this regard, discovering new effective radioprotectors as well as novel principles of protecting living organisms from high-dose radiation is the most important factor, determining the new approaches in medical and technical usage of radiation. Materials and methods: Experimental animals were irradiated on the γ-emitter (Cs137) with a dose of 9.4 Gy. Radioprotective properties of several agents (total RNA, single-stranded RNA, double-stranded RNA and B-190) were estimated by the survival/death rates of experimental animals within 30–90 d. Pathomorphological examination of internal organs end electron microscope assay was done on days 9–12 after irradiation. Cloning and other molecular procedures were performed accordingly to commonly accepted protocols. For assessment of the internalization of labeled nucleic acid, bone marrow cells were incubated with double-stranded RNA labeled with 6-FAM fluorescent dye. Cells with internalized double-stranded RNA were assayed using Axio Imager M1 microscope. In the other experiment, bone marrow cells after incubation with double-stranded RNA were stained with Cy5-labeled anti-CD34 antibodies and assayed using Axioskop 2 microscope. Results: In this study, several biological features of the radioprotective action of double-stranded RNA are characterized. It was shown that 160 µg of the double-stranded RNA per mouse protect experimental animals from the absolutely lethal dose of γ-radiation of 9.4 Gy. In different experiments, 80–100% of irradiated animals survive and live until their natural death. Radioprotective properties of double-stranded RNA were found to be independent on its sequence, but strictly dependent on its double-stranded form. Moreover, double-stranded RNA must have ‘open’ ends of the molecule to exert its radioprotective activity. Conclusions: Experiments indicate that radioprotective effect of double-stranded RNA is tightly bound to its internalization into hematopoietic stem cells, which further repopulate the spleen parenchyma of irradiated mice. Actively proliferating progenitors form the splenic colonies, which further serve as the basis for restoration of hematopoiesis and immune function and determine the survival of animals received the lethal dose of radiation.

AB - The purpose of the article: Protection from ionizing radiation is the most important component in the curing malignant neoplasms, servicing atomic reactors, and resolving the situations associated with uncontrolled radioactive pollutions. In this regard, discovering new effective radioprotectors as well as novel principles of protecting living organisms from high-dose radiation is the most important factor, determining the new approaches in medical and technical usage of radiation. Materials and methods: Experimental animals were irradiated on the γ-emitter (Cs137) with a dose of 9.4 Gy. Radioprotective properties of several agents (total RNA, single-stranded RNA, double-stranded RNA and B-190) were estimated by the survival/death rates of experimental animals within 30–90 d. Pathomorphological examination of internal organs end electron microscope assay was done on days 9–12 after irradiation. Cloning and other molecular procedures were performed accordingly to commonly accepted protocols. For assessment of the internalization of labeled nucleic acid, bone marrow cells were incubated with double-stranded RNA labeled with 6-FAM fluorescent dye. Cells with internalized double-stranded RNA were assayed using Axio Imager M1 microscope. In the other experiment, bone marrow cells after incubation with double-stranded RNA were stained with Cy5-labeled anti-CD34 antibodies and assayed using Axioskop 2 microscope. Results: In this study, several biological features of the radioprotective action of double-stranded RNA are characterized. It was shown that 160 µg of the double-stranded RNA per mouse protect experimental animals from the absolutely lethal dose of γ-radiation of 9.4 Gy. In different experiments, 80–100% of irradiated animals survive and live until their natural death. Radioprotective properties of double-stranded RNA were found to be independent on its sequence, but strictly dependent on its double-stranded form. Moreover, double-stranded RNA must have ‘open’ ends of the molecule to exert its radioprotective activity. Conclusions: Experiments indicate that radioprotective effect of double-stranded RNA is tightly bound to its internalization into hematopoietic stem cells, which further repopulate the spleen parenchyma of irradiated mice. Actively proliferating progenitors form the splenic colonies, which further serve as the basis for restoration of hematopoiesis and immune function and determine the survival of animals received the lethal dose of radiation.

KW - B-190

KW - double-strand breaks

KW - Double-stranded RNA

KW - spleen colonies

KW - STEM-CELLS

KW - ACTIVATION

KW - CYTOKINES

KW - MECHANISM

KW - MOUSE

KW - INDUCED GENOMIC INSTABILITY

KW - IONIZING-RADIATION

KW - DNA-REPAIR

KW - METHYLGLYOXAL

KW - EXPOSURE

UR - http://www.scopus.com/inward/record.url?scp=85088827783&partnerID=8YFLogxK

U2 - 10.1080/09553002.2020.1793020

DO - 10.1080/09553002.2020.1793020

M3 - Article

C2 - 32658564

AN - SCOPUS:85088827783

VL - 96

SP - 1173

EP - 1191

JO - International Journal of Radiation Biology

JF - International Journal of Radiation Biology

SN - 0955-3002

IS - 9

ER -