Characterization of biological peculiarities of the radioprotective activity of double-stranded RNA isolated from<i>Saccharomyces сerevisiae</i>

Ritter, Genrikh S.; Николин, В. П.; Попова, Н. А.; Proskurina, Anastasia S.; Kisaretova, Polina E.; Taranov, Oleg S.; Dubatolova, T. D.; Долгова, Е. В.; Potter, Ekaterina A.; Кирикович, С. С.; Efremov, Yaroslav R.; Bayborodin, Sergey I.; Romanenko, Margarita V.; Meschaninova, Mariya I.; Ven’yaminova, A. G.; Kolchanov, Nikolay А.; Shurdov, Mikhail A.; Bogachev, Sergey S.

doi:10.1080/09553002.2020.1793020

Cited by 5 publications

(6 citation statements)

References 54 publications

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“…Thorough examination of this process revealed no signs of active cell migration, such as pseudopodia formation and others, and thus might testify to the Coulomb attraction of differently charged cells ( Figures 1A–C ) ( Dolgova et al, 2016b , 2019 ). Moreover, in cytological preparations of mouse bone marrow, structures constituted of cell aggregates with TAMRA+/c-Kit/Sca1/CD34+ (HSCs and their multipotent progeny with internalized TAMRA-labeled dsDNA probe) cells in their center were always observed ( Dolgova et al, 2013 ; Ritter et al, 2020 ) ( Figures 1D,E ). Such a structure could be a result of the stem niche preformation, during which the stem cell attracts and fixes stromal cells around itself.…”

Section: Introductionmentioning

confidence: 98%

The new general biological property of stem-like tumor cells Part I. Peculiarities of the process of the double-stranded DNA fragments internalization into stem-like tumor cells

Ritter

Долгова²,

Petrova³

et al. 2022

Front. Genet.

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Stem-like tumor cells of ascites carcinoma Krebs-2 and Epstein-Barr virus–induced B-lymphoma were shown to possess the innate capability of binding and internalizing the TAMRA-labeled double-stranded DNA (dsDNA) probe. The process of binding and internalizing is rather complicated and composed of the following successive stages: 1) initiating electrostatic interaction and contact of a negatively charged dsDNA molecule with a positively charged molecule(s) on the surface of a stem-like tumor cell; 2) binding of the dsDNA probe to a tumor stem cell surface protein(s) via the formation of a strong chemical/molecular bond; and 3) the very internalization of dsDNA into the cell. Binding of DNA to cell surface proteins is determined by the presence of heparin/polyanion-binding sites within the protein structure, which can be competitively blocked by heparin and/or dextran sulfate, wherein heparin blocks only the binding, while dextran sulfate abrogates both binding and internalization. The abrogation of internalization by dextran sulfate implies the role of scavenger receptors in this process. Cells were shown to uptake DNA in amounts constituting ∼0.008% of the haploid genome. Inhibitors of caveolae-dependent internalization abrogate the DNA uptake in Krebs-2 cells, and inhibitors of the clathrin/caveolar mechanism block the internalization in B-lymphoma cells. In the present report, it is shown for the first time that in contrast to the majority of committed tumor cells, stem-like tumor cells of Krebs-2 and B-lymphoma carry a general positive charge on their surface.

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Section: Introductionmentioning

confidence: 98%

The new general biological property of stem-like tumor cells Part I. Peculiarities of the process of the double-stranded DNA fragments internalization into stem-like tumor cells

Ritter

Долгова²,

Petrova³

et al. 2022

Front. Genet.

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“…Based on the results we have obtained, it can be presumed that the radioprotective effect of dsRNA has an alternative origin and is associated with its role in facilitating the process of double-stranded brakes repair in bone marrow progenitor cells (17,(29)(30)(31) , which, in turn, ensures preservation of hematopoietic progenitors and quick restoration of all of hematopoiesis.…”

Section: Discussionmentioning

confidence: 88%

“…Total yeast RNA was purchased from Biolar Company, Russia. dsRNA was obtained by the hydroxyapatite chromatographic fractionation of total yeast RNA under standard condition as described in (17) .…”

Section: Rna Preparationsmentioning

confidence: 99%

“…In our recent studies (16,17) , yeast double-stranded RNA (dsRNA) showed pronounced radioprotective and moderate radiotherapeutic effects on deadly (9.4 Gy) irradiated mice. It was shown that the protection of animals against lethal irradiation was associated with the preservation of CD34+ hematopoietic stem cells, their migration to peripheral lymphoid organs (spleen) and the formation of new nodes with actively proliferating immune cells.…”

Section: Introductionmentioning

confidence: 99%

“…It was shown that the protection of animals against lethal irradiation was associated with the preservation of CD34+ hematopoietic stem cells, their migration to peripheral lymphoid organs (spleen) and the formation of new nodes with actively proliferating immune cells. Analysis of bone marrow cells and splenic colonies showed that the treatment with Saccharomyces cerevisiae RNA is accompanied by the preservation of both leukocytic and erythroid lineages (17) .…”

Section: Introductionmentioning

confidence: 99%

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Changes in the number and morphology of blood cells in mice pretreated with RNA preparations and exposed to 8 Gy of gamma radiation

Dubatolova

Ritter²,

Proskurina³

et al. 2022

Int J Radiat Res

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Background:In our recent studies, yeast double-stranded RNA showed radioprotective effect in mice exposed to 9.4 Gy of gamma radiation. The current work continues our inquiry and describes the changes in the number and morphology of blood cells in mice injected with double-stranded RNA from Saccharomyces cerevisiae prior to gamma irradiation. To be capable of estimating the required parameters, we have used 8 Gy of radiation, which allowed mice to survive for up to 37 days (LD60/30). Materials and Methods: Animals received single intravenous injections of one of the following compounds: (1) 7 mg of total RNA isolated from baking yeast Saccharomyces cerevisiae, (2) 200 μg of double-stranded RNA or (3) 400 μg of doublestranded RNA. 30 minutes later, using a 137 Cs gamma emitter, mice were irradiated with a dose of 8 Gy at the rate of 1.4 Gy/min. The radioprotective effect of preparations was assessed based on death rates. Results: Injections of both 200 μg of double-stranded RNA and 7 mg of total RNA prior to irradiation provided the best radioprotective effects, ensuring the survival of 100% of animals. Changes in the number of blood cells and their morphological aberrations were being monitored for 37 days after irradiation. Conclusion: The protection from lethal radiation doses is associated with the preservation and rapid recovery of leukocytic and erythroid lineages.

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Development of an Optimal Model of Combined Radiation and Biological Lesions

Gaynutdinov¹,

Vagin²,

Kurbangaleev³

et al. 2022

Veterinary Medicine International

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Since the search for the effective medication in combined lesions includes the selection of an optimal experimental model for such injuries, there is actually a study aimed at developing an optimal model of combined radiation-biology (Pasteurella) lesions. The pathogen Pasteurella multocida (as one of the most frequent pathogenic agents involved in both isolated and combined radiation-biology lesions of agricultural animals) was used as a model of a biological agent to reproduce experimental biological research. We employed the “Chinchilla” rabbits of 2.5–3.0 kg body weight as a biological model for doing combined radiation Pasteurella lesion. When determining the optimal model of combined radiation-biology (Pasteurella) lesion, we consider that in the joint action of various pathological agents on the organism, there is a synergistic effect of explosion agents, previously specifying minimal doses of external γ-radiation and pasteurellosis pathogen that in the joint action of nonfatal doses would be lethal. The first stage of the experiments determined the minimal doses of gamma rays and pasteurellosis pathogen that in joint action causes combined radiation-biology pathology. We examined 66 rabbits divided into 11 groups of 6 animals each to determine minimal doses of infectious agent-pasteurellosis pathogen. The animals of the first 9 groups were given subcutaneously Pasteurella species at doses 1·109, 1·108, 1·107, 1·106, 1·105, 1·104, 1·103, 1·102, and 1·101 of microbial cells per animal of 0.3 ml suspension in volume; the 10th group of animals were given saline solution; the 11th served as a biological control group. In determining the minimal doses of gamma rays, we conducted experimental tests on 36 rabbits, which have been exposed to external γ-radiation in the “PUMA” system with a 137Cs radiation source of the exposure dose of 5.38 R/min at doses 2.0, 4.0, 6.0, 8.0, 10, and 12 Gy. To specify the optimal model of radiation-pasteurellosis lesion, we used the rabbits subjected to a combined radiation-biology effect using minimal doses of gamma rays and pasteurellosis agent, leading to a lethal effect during their complex action. The researches revealed that 50% of the death of rabbits infected with pasteurellosis occurs using Pasteurella at a dose of 3.7·104 microbial cells per kilogram (LD50 = 3.7∙104 m.c./kg), and 50% of radiation death in rabbits occurs when irradiated their gamma rays at a dose of 8.0 Gy (LD50 = 8.0 Gy). The combined effect of nonlethal doses of the studied agents in the indicated doses on rabbits led to the aggravation of the course of radiation and pasteurellosis infection, causing the death of animals from combined radiation-pasteurellosis pathology. The model combined radiation-pasteurellosis disease ran its course rapidly, and the animals died 3 to 6 days after the onset. The autopsy of the animals that died from acute radiation-pasteurellosis pathogen had found swelling of the subcutaneous tissue in the pharynx and intermaxillary space of the neck, hyperemia, lymphoid nodular hyperplasia, numerous hemorrhages on the serous and mucous membranes and in the tissues of the parenchymal organs, serous or serous-fibrinous exudate, and in the chest and abdominal regions, pulmonary edema. The research stated that gamma radiation of rabbits at a dose of 8.0 Gy conducted before exposure with Pasteurella at LD50 (3.7·104 m.c./kg) declined the course of the pasteurellosis process, facilitated its generalization, and fastened the death of animals. Combined radiation-pasteurellosis infection ran its course rapidly, and the animals died within 3 to 6 days after the onset of the disease. The autopsy showed the pathologicoanatomic factors of the acute pasteurellosis: swelling of the subcutaneous tissue, purulent-catarrhal bronchopneumonitis, and pulmonary edema.

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

Cited by 5 publications

References 54 publications

The new general biological property of stem-like tumor cells Part I. Peculiarities of the process of the double-stranded DNA fragments internalization into stem-like tumor cells

The new general biological property of stem-like tumor cells Part I. Peculiarities of the process of the double-stranded DNA fragments internalization into stem-like tumor cells

Changes in the number and morphology of blood cells in mice pretreated with RNA preparations and exposed to 8 Gy of gamma radiation

Development of an Optimal Model of Combined Radiation and Biological Lesions

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