The antimutagenic activity of anti-radiation drugs betaleukin, flagellin, indraline and riboxin with different mechanisms of action was studied in short-term and chronic experiments in mice in vivo. All drugs showed antimutagenic properties in bone marrow cells, as well as hepatoprotective effect. The greatest effect under the used experimental conditions was noted for betaleukin and the new anti-radiation drug flagellin.

We used 183 F1 CBA×C57Bl hybrid mice to study the delayed effects of low-power long-term γ-irradiation at a dose of 12.6 Gy (10 mGy/min) 8 and 10 months after the treatment. Eight months after the treatment we found the increased expression of the transcription factor NFκB and its target genes iNOS and G-SCF in the bone marrow (BM). Ten months after the treatment malignant lymphomas were revealed in 14 of 94 mice in the liver, abdominal cavity, and subcutaneously. In the BM of these mice, the transcription of the PTEN, NFκB, and iNOS genes was inhibited and the contents of long non-coding RNAs (lncRNAs) lnc p21, NEAT1, and microRNA miR-125b were decreased. The expression of the NFκB(p65) gene and miR-125b was inhibited in the BM of irradiated mice without tumors ten months after the treatment. These data show the deregulation of the P53 system supporting the genome stability in the BM of irradiated mice. These indices will be studied as potential markers of risk of development of irradiation-induced tumors.

Изучена антимутагенная активность противолучевых препаратов разного механизма действия: беталейкина, флагеллина, индралина и рибоксина в краткосрочных и хроническом экспериментах на мышах in vivo. Все препараты проявили антимутагенные свойства в клетках костного мозга, а также гепатопротекторное действие. Наибольший эффект при используемых условиях эксперимента отмечен для беталейкина и нового противолучевого препарата флагеллина. The antimutagenic activity of anti-radiation drugs betaleukin, flagellin, indraline and riboxin with different mechanisms of action was studied in short-term and chronic experiments in mice in vivo. All drugs showed antimutagenic properties in bone marrow cells, as well as hepatoprotective effect. The greatest effect under the used experimental conditions was noted for betaleukin and the new anti-radiation drug flagellin.

We studied the radioprotective effect of betaleukin administered to (CBA×C57Bl/6)F1 mice in single doses of 50 and 3 μg/kg 2 and 22 h, respectively, prior to long-term (21 h) whole-body low-intensity (10 mGy/min) γ-radiation (137Сs; total dose 12.65 Gy). Hepatocyte ploidy, a biomarker of metabolic disorders of the liver, was evaluated, and nuclearity and ploidy indices were calculated. In 10 months after irradiation, a significant decrease in the ploidy index was revealed in the group of irradiated mice, while in animal receiving 3 or 50 μg/kg betaleukin, this parameter did not differ and even surpassed the control level, respectively. Thus, in vivo assessment of hepatocytic ploidy profile in mice revealed negative delayed effects of γ-irradiation in a dose of 12.65 Gy and a protective effect a single injection of immunomodulator betaleukin.

We studied the mutagenic effect of X-ray irradiation in doses of 0.5, 1, and 1.5 Gy on female (CBA×C57Bl/6)F1 mice. The mutagenic effect (assessed by the parameter “frequency of bone marrow polychromatophilic erythrocytes with micronuclei”) linearly depended on the dose of X-ray irradiation in the range of up to 1 Gy and reached the plateau at 1.5 Gy. The fraction of polychromatophilic erythrocytes was 45, 45, and 46% under control conditions (without exposure) and exposure to the irradiation in the doses of 0.5 and 1 Gy, respectively. Irradiation in a dose of 1.5 Gy induced a slight inhibition of erythropoiesis. These data confirm the hypothesis on possible death of highly aberrant erythrocyte precursors after irradiation in high doses.