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

Genrikh S. Ritter, Valeriy P. Nikolin, Nelly A. Popova, Anastasia S. Proskurina, Polina E. Kisaretova, Oleg S. Taranov, Tatiana D. Dubatolova, Evgenia V. Dolgova, Ekaterina A. Potter, Svetlana S. Kirikovich, Yaroslav R. Efremov, Sergey I. Bayborodin, Margarita V. Romanenko, Maria I. Meschaninova, Aliya G. Venyaminova, Nikolay A. Kolchanov, Mikhail A. Shurdov, Sergey S. Bogachev

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1173-1191
Number of pages19
JournalInternational Journal of Radiation Biology
Volume96
Issue number9
DOIs
StatePublished - Sep 1 2020

Bibliographical note

Funding Information:
The work was supported by the Russian Ministry of Science and High Education via the Institute of Cytology and Genetics [state budget project No 0324-2019-0042-C-01, state registration No AAAA-A17-117071240065-4] and Russian Foundation for Basic Research [grant No 18-34-00205]. Microscopy analysis was supported by the Russian State-funded budget project of the Institute of Molecular and Cellular Biology SB RAS [No 0310-2019-0005]. The RNA?s chemical synthesis work was supported by the Russian State-funded budget project of the Institute of Chemical Biology and Fundamental Medicine SB RAS [No AAAA-A17-117020210021-7]. The authors express their gratitude to Prof. Sergey V. Netesov for technical support, the laboratory of immunogenetics of the Institute of Molecular and Cellular Biology SB RAS for providing XL1-Blue MRF cells, the Radioisotope Division of ICG SB RAS, the Flow Cytometry Shared Facility ICG SB RAS, and the Common Use Center for Microscopy of Biologic Objects SB RAS.

Publisher Copyright:
© Copyright © 2020 Taylor & Francis Group LLC.

Keywords

  • B-190
  • Double-stranded RNA
  • double-strand breaks
  • spleen colonies

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