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.
Acknowledgments
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.
Disclosure statement
The authors report no conflict of interest.
Additional information
Funding
Notes on contributors
Genrikh S. Ritter
Genrikh S. Ritter have graduated from Novosibirsk State University. Now he is a PhD student and Researcher of the Laboratory of induced cellular processes in the Institute of Cytology and Genetics.
Valeriy P. Nikolin
Valeriy P. Nikolin have graduated from Novosibirsk State Medical University. He is a PhD and has many years of experience working with experimental animals.
Nelly A. Popova
Nelly A. Popova have graduated from Novosibirsk State Medical University. She is a PhD and Professor of Novosibirsk State University.
Anastasia S. Proskurina
Anastasia S. Proskurina have graduated from Novosibirsk State University. She is a PhD and the Senior Research Associate of the Laboratory of induced cellular processes in the Institute of Cytology and Genetics.
Polina E. Kisaretova
Polina E. Kisaretova have graduated from Novosibirsk State University. Now she is a PhD student.
Oleg S. Taranov
Oleg S. Taranov is the Head of the Department of Microscopic Research in the State Research Center of Virology and Biotechnology “Vector”. He has many years of experience in pathomorphological assay and electron microscopy.
Tatiana D. Dubatolova
Tatiana D. Dubatolova is a Researcher of Institute of Molecular and Cellular Biology and has many years of experience in microscopic analysis of blood cells.
Evgenia V. Dolgova
Evgenia V. Dolgova have graduated from Novosibirsk State University. She is a PhD and the Senior Research Associate of the Laboratory of induced cellular processes in the Institute of Cytology and Genetics.
Ekaterina A. Potter
Ekaterina A. Potter have graduated from Novosibirsk State University. She is a PhD and the Senior Research Associate of the Laboratory of induced cellular processes in the Institute of Cytology and Genetics.
Svetlana S. Kirikovich
Svetlana S. Kirikovich is a PhD and the Research Associate of the Laboratory of induced cellular processes in the Institute of Cytology and Genetics.
Yaroslav R. Efremov
Yaroslav R. Efremov have graduated from Novosibirsk State University. He is a PhD and an Engineer at the Flow Cytometry Shared Facility ICG SB RAS.
Sergey I. Bayborodin
Sergey I. Bayborodin have graduated from Novosibirsk State University. He is a PhD and the head of the Common Use Center for Microscopy of Biologic Objects SB RAS.
Margarita V. Romanenko
Margarita V. Romanenko have graduated from Novosibirsk State University. She is a PhD and the Research Associate of the Novosibirsk State University.
Maria I. Meschaninova
Maria I. Meschaninova is a PhD and the Research Associate of the RNA Chemistry Laboratory in the Institute of Chemical Biology and Fundamental Medicine.
Aliya G. Venyaminova
Aliya G. Venyaminova is a PhD and the Head of the RNA Chemistry Laboratory in the Institute of Chemical Biology and Fundamental Medicine.
Nikolay A. Kolchanov
Nikolay A. Kolchanov have graduated from Novosibirsk State University. He was the Director of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences from 2008 to 2018 years. He is an Academician of the Russian Academy of Sciences and professor of Novosibirsk State University.
Mikhail A. Shurdov
Mikhail A. Shurdov have graduated from Novosibirsk State University. He is a PhD and the head of the Joint Stock Company “Cheboksary Electrical Apparatus Plant”.
Sergey S. Bogachev
Sergey S. Bogachev have graduated from Saratov State University. He is a Doctor of Science and the head of the Laboratory of induced cellular processes in the Institute of Cytology and Genetics.