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Characterization of biological peculiarities of the radioprotective activity of double-stranded RNA isolated from Saccharomyces сerevisiae.
International Journal of Radiation Biology ( IF 2.6 ) Pub Date : 2020-07-28 , DOI: 10.1080/09553002.2020.1793020
Genrikh S Ritter 1, 2 , Valeriy P Nikolin 1 , Nelly A Popova 1, 2 , Anastasia S Proskurina 1 , Polina E Kisaretova 1 , Oleg S Taranov 3 , Tatiana D Dubatolova 4 , Evgenia V Dolgova 1 , Ekaterina A Potter 1 , Svetlana S Kirikovich 1 , Yaroslav R Efremov 1, 2 , Sergey I Bayborodin 1, 2 , Margarita V Romanenko 2 , Maria I Meschaninova 5 , Aliya G Venyaminova 5 , Nikolay A Kolchanov 1 , Mikhail A Shurdov 6 , Sergey S Bogachev 1
Affiliation  

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.



中文翻译:

从啤酒酵母分离的双链RNA的放射防护活性的生物学特性的表征。

文章目的

防止电离辐射是治愈恶性肿瘤,维修原子反应堆以及解决与不受控制的放射性污染有关的情况的最重要组成部分。在这方面,发现新的有效辐射防护剂以及保护活生物体免受大剂量辐射的新原理是最重要的因素,决定了辐射医学和技术用途的新方法。

材料和方法

在γ发射体上照射实验动物(Cs 137),剂量为9.4 Gy。通过实验动物在30-90 d内的存活/死亡率来评估几种试剂(总RNA,单链RNA,双链RNA和B-190)的辐射防护特性。内脏电子显微镜检查的病理形态学检查在照射后第9-12天进行。根据普遍接受的方案进行克隆和其他分子程序。为了评估标记的核酸的内在化,将骨髓细胞与用6-FAM荧光染料标记的双链RNA孵育。使用Axio Imager M1显微镜分析具有内化双链RNA的细胞。在另一个实验中,将与双链RNA孵育后的骨髓细胞用Cy5标记的抗CD34抗体染色,并使用Axioskop 2显微镜进行分析。

结果

在这项研究中,表征了双链RNA的放射防护作用的几个生物学特征。结果表明,每只小鼠160 µg的双链RNA可保护实验动物免受9.4 Gy的绝对致命剂量的γ辐射的伤害。在不同的实验中,受辐照的动物中有80-100%存活并存活到自然死亡。发现双链RNA的放射防护性质不依赖于其序列,但是严格依赖于其双链形式。此外,双链RNA必须具有分子的“开放”末端才能发挥其放射防护活性。

结论

实验表明,双链RNA的放射防护作用与其内化成造血干细胞紧密结合,从而进一步使受辐照小鼠的脾实质重新分布。活跃增殖的祖细胞形成脾脏集落,它们进一步充当恢复造血作用和免疫功能的基础,并确定接受致死剂量辐射的动物的存活率。

更新日期:2020-08-27
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