Medical Radiology and Radiation Safety. 2025. Vol. 70. № 5

DOI:10.33266/1024-6177-2025-70-5-11-17

E.A. Mysina, D.D. Kolmanovich, N.R. Popova, B.A. Bokl, 
N.A. Pivovarov, N.N. Chukavin, I.V. Savintseva, D.A. Vinnik, A.L. Popov

3D Cell Spheroid as a Relevant Experimental Model for Screening Potential Nanoradiosensitizers

Institute of Theoretical and Experimental Biophysics, Pushchino, Russia

Contact person: A.L. Popov, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Abstract

Purpose: Cell monolayer (2D culture) has been used to screen biological activity of various biomolecules, nanoconjugates, and other therapeutic agents. However, 2D cell culture cannot fully imitate real physiological structures and states of the human body, in particular, the organization and microenvironment of a solid tumor. This imposes significant limitations on current translational studies of the biological effect of new therapeutic drugs and approaches to tumor radiation therapy. To overcome these limitations, models based on 3D cell spheroids are developed and put into practice. These models allow the most reliable imitation of the structure and state of a solid tumor, including the formation of 3D intercellular matrix, characteristic zonation, and corresponding gene expression.

Purpose of the investigation: To create an experimental model of a 3D spheroid formed on the basis of mouse breast cancer cells EMT6/P line and validate the model under X-ray exposure for screening potential nanoradiosensitizers.

Material and methods: The EMT6/P cell line (mouse carcinoma) was used to form a 3D cell spheroid and evaluate the biological effect of X-ray radiation on it. Cell spheroids were prepared using the "hanging drop" method. An RUT-15 X-ray machine was used to irradiate the spheroids. The radiation doses varied from 0 to 10 Gy. After irradiation, cell viability was analyzed by flow cytometry. Staining was performed with a set of fluorescent dyes Annexin V-FITC/propidium iodide. The migration activity of irradiated spheroid cells was assessed by confluent analysis after transferring the spheroid to adhesive plastic.

Results: A dose-dependent decrease in cell migration activity was shown after X-ray irradiation in the dose range of 1–10 Gy. It has been established that doses of 6–8 Gy are optimal for the analysis of potential radiosensitizers by assessing the migration activity of cells. Using citrate-stabilized cerium oxide (CeO₂) nanoparticles as an example, the possibility of using this model for rapid screening of nanomaterials with radiosensitizing action is demonstrated.

Conclusion: A method for forming 3D cell spheroids from EMT6/P cells has been developed and validated. The optimal dose of X-ray irradiation of the resulting cell spheroid has been selected for rapid screening of potential radiosensitizers. The functionality and reproducibility of the developed experimental model have been confirmed.

Keywords: 3D cell spheroid, solid tumor model, X-ray irradiation, radiosensitization

For citation: Mysina EA, Kolmanovich DD, Popova NR, Bokl BA, Pivovarov NA, Chukavin NN, Savintseva IV, Vinnik DA, Popov AL. 3D Cell Spheroid as a Relevant Experimental Model for Screening Potential Nanoradiosensitizers. Medical Radiology and Radiation Safety. 2025;70(5):11–17. (In Russian). DOI:10.33266/1024-6177-2025-70-5-11-17

 

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14. Ivanova O.S., Shekunova T.O., Ivanov V.K., Shcherbakov A.B., Popov A.L., Davydova G.A., Selezneva I.I., Kopitsa G.P., Tret’yakov Yu.D. One-Stage Synthesis of Ceria Colloid Solutions for Biomedical Use. Doklady Chemistry. 2011;437;2:103-106.

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22. Kornienko A.I., Teplonogova M.A., Shevelyova M.P., Popkov M.A., Popov A.L., Ivanov V.E., Popova N.R. Novel Flavin Mononucleotide-Functionalized Cerium Fluoride Nanoparticles for Selective Enhanced X-Ray-Induced Photodynamic Therapy. Journal of Functional Biomaterials. 2024;15;12:373.

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 PDF (RUS) Full-text article (in Russian)

 

Conflict of interest. The authors declare no conflict of interest.

Financing. The article was prepared as part of the RSCF grant No 22-73-10231, https://rscf.ru/project/22-73-10231/.

Contribution. E.A. Mysina – work with spheroids (cultivation, irradiation, viability analysis), D.D. Kolmanovich – flow cytometry and data analysis, N.R. Popova – scientific text editing, B.A. Bokle – collection and analysis of literary material, N.A. Pivovarov– collection and analysis of literary material, N.N. Chukavin – scientific text editing, I.V. Savintseva– cell culture, D.A. Vinnik – spheroid irradiation, A.L. Popov – research design development, scientific guidance.

Article received: 20.05.2025. Accepted for publication: 25.06.2025.

 

Medical Radiology and Radiation Safety. 2025. Vol. 70. № 5

DOI:10.33266/1024-6177-2025-70-5-23-27

M.A. Ignatov^{1, 2}, A.K. Chigasova^{1, 2, 3}, A.A. Osipov², N.Yu. Vorobyeva^{1, 2},
Yu.A. Fedotov^{1, 2}, Dn.M. Alekseev¹, T.I. Gimadova¹, А.N. Bashkov¹,
Yu.D. Udalov¹,  A.N. Osipov^{1, 2} 

Changes in the Number of Dna Repair Protein Foci in Tomography-Irradiated Human Mesenchymal Stem Cells

¹ A.I. Burnazyan Federal Medical Biophysical Center, Moscow, Russia

² N.N. Semenov Federal Research Center for Chemical Physics, Moscow, Russia 

³ Institute of Biochemical Physics, Moscow, Russia

Contact person: A.N. Osipov, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Abstract

Purpose: Comparative analysis of changes in the number of γH2AX, 53BP1 and pATM foci in human mesenchymal stem/stromal cells (MSCs) after irradiation during single and five-time sequential computed tomography (CT). Additionally, as a positive control, changes in these parameters were studied after irradiation of cells using an X-ray machine at a dose of 2000 mGy.

Material and methods: A primary culture of human MSCs was obtained from the collection of BioloT LLC (Russia). A TOSHIBA AQUILION 64 computed tomograph (Japan) was used for cell irradiation. Dosimetric monitoring was carried out using the thermoluminescent method with aluminophosphate dosimeters and magnesium borate-based dosimeters. For comparative studies and obtaining a positive control, a RUST-M1 X-ray biological unit (Russia) equipped with two X-ray emitters (dose 2000 mGy, dose rate 0.85 Gy/min) was used. Immunocytochemical staining using antibodies to γH2AX, 53BP1 and pATM was used for quantitative assessment of γH2AX, 53BP1 and pATM foci. Statistical significance was assessed using analysis of variance (ANOVA).

Results: The studies showed that irradiation of MSCs during CT (absorbed doses during single CT approximetly 88 mGy) causes a statistically significant increase in the number of foci of the proteins γH2AX, 53BP1 and pATM, recorded 0.5 h after irradiation. However, no statistically significant increase in the number of residual γH2AX, 53BP1 and pATM foci was observed 24 h after irradiation compared to the control values. In general, a comprehensive assessment of the number of γH2AX, 53BP1 and pATM protein foci can be recommended for early biodosimetry of irradiation during CT.

Keywords: computed tomography, x-ray radiation, low doses, mesenchymal stem cells, DNA repair, γH2AX, 53BP1, pATM

For citation: Ignatov MA, Chigasova AK, Osipov AA, Vorobyeva NYu, Fedotov YuA, Alekseev DnM, Gimadova TI, Bashkov АN, Udalov YuD, Osipov AN. Changes in the Number of Dna Repair Protein Foci in Tomography-Irradiated Human Mesenchymal Stem Cells. Medical Radiology and Radiation Safety. 2025;70(5):23–27. (In Russian). DOI:10.33266/1024-6177-2025-70-5-23-27

 

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 PDF (RUS) Full-text article (in Russian)

 

Conflict of interest. The authors declare no conflict of interest.

Financing. The research was supported by the Russian Science Foundation (project No. 23-14-00078).

Contribution. Article was prepared with equal participation of the authors.

Article received: 20.05.2025. Accepted for publication: 25.06.2025.

 

Medical Radiology and Radiation Safety. 2025. Vol. 70. № 5

DOI:10.33266/1024-6177-2025-70-5-18-22

A.Yu. Bushmanov, V.Yu. Soloviev, V.V. Zorin, O.V. Nikitenko, T.M. Bychkova,
A.O. Lebedev, A.A. Ivanov , Yu.A. Zrilova, T.A. Astrelina, V.A. Brunchukov,
L.M. Rozhdestvenskyj, Yu.A. Fedotov, T.I. Gimadova, L.Yu. Mershin, A.S. Kretov,
T.G. Shlyakova, A.N. Osipov

Evaluation of the Effectiveness of the Drug Indralin in the Irradiation of Small, Medium and Large Laboratory Animals with Gamma Radiation

A.I. Burnazyan Federal Medical Biophysical Center, Moscow, Russia

Contact person: V.Yu. Soloviev, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

ABSTRACT

Purpose: Evaluation of the effectiveness of the drug indralin in experiments with small, medium and large laboratory animals.

Material and methods: The objects of the study were outbred male mice of the ICR (CD-1) SPF category, rabbits of the “Soviet Chinchilla” breed, mini-pigs of the Svetlogorsk breed and beagle dogs. The experimental animals were kept in conventional conditions, on standard granulated feed and tap drinking water. During the studies, the radionuclide installation GUT200M (⁶⁰Co) and the installation for generating bremsstrahlung X-rays based on the pulsed linear resonance electron accelerator ILU-14 were used as radiation sources. Mice, mini-pigs and dogs were irradiated using the GUT200M (⁶⁰Co) installation, rabbits – using the ILU-14 installation. The radiation dose was controlled by thermoluminescent dosimeters in the individual dosimetry support mode. The biological effect was assessed in terms of 30-day survival for mice and rabbits and 45-day survival for large laboratory animals (mini-pigs and dogs). At the first stage, the dose-effect relationship was assessed for all experimental animals, and the irradiation conditions that ensured 80-90% mortality of animals were assessed. At the second stage, the effectiveness of indralin was assessed.

Results: The following estimates were obtained: LD_50/30: mice – 7.9±0.2, rabbits – 9.6±0.3; LD_50/45: mini-pigs – 2.7±0.2 Gy, dogs – 2.4±0.3 Gy; LD_84/30: mice – 8.7±0.4 Gy, rabbits – 10.0±0.2 Gy; LD_84/45: mini-pigs – 3.1±0.2 Gy, dogs – 3.2±0.2 Gy. In the experiment on mice: when irradiated at doses of 8.7 and 10.3 Gy, there were no surviving mice in the control, while when using indralin, the proportion of surviving animals was 68 % and 38 %, respectively. In the experiment on mini-pigs: in the control 9 % survived, with indralin – 75 %; for dogs: in the control 14 % survived, with indralin – 86 %. In the experiment on rabbits, the positive effect was insignificant: there were no survivors in the control, while when using indralin at a dose of 21 mg/kg, the proportion of survivors was 15 %, and at a dose of 37.5 mg/kg – 25 %.

Conclusion: In an experiment on small, medium and large laboratory animals, the high efficiency of the drug indralin was confirmed when used in regulated doses 10–15 minutes before irradiation.

Keywords: X-rays, laboratory animals, survival, radioprotective drugs, indralin

For citation: Bushmanov AYu, Soloviev VYu, Zorin VV, Nikitenko OV, Bychkova TM, Lebedev AO, Ivanov AA, Zrilova YuA, Astrelina TA, Brunchukov VA, Rozhdestvenskyj LM, Fedotov YuA, Gimadova TI, Mershin LYu, Kretov AS, Shlyakova TG, Osipov AN. Evaluation of the Effectiveness of the Drug Indralin in the Irradiation of Small, Medium and Large Laboratory Animals with Gamma Radiation. Medical Radiology and Radiation Safety. 2025;70(5):18–22. (In Russian). DOI:10.33266/1024-6177-2025-70-5-18-22

 

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 PDF (RUS) Full-text article (in Russian)

 

Conflict of interest. The authors declare no conflict of interest.

Financing. The study had no sponsorship.

Contribution. Article was prepared with equal participation of the authors.

Article received: 20.05.2025. Accepted for publication: 25.06.2025.

 

Medical Radiology and Radiation Safety. 2025. Vol. 70. № 5

DOI:10.33266/1024-6177-2025-70-5-28-35

E.A. Kodintseva¹, A.А. Akleyev²

The Contribution of Effector Cells of the Innate and Adaptive Immunity to the Pathogenesis of Radiation-Induced Carcinogenesis. Review (Part 2)

¹ Urals Research Center for Radiation Medicine, Chelyabinsk, Russia

² Southern-Urals State Medical University, Chelyabinsk, Russia

Contact person: E.A. Kodintseva, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

CONTENTS

 

Background

1. Cooperation of innate and adaptive immunity cells in pathogenesis in carcinogenesis

2. Neutrophilic granulocytes and cytotoxic T-lymphocytes

3. Neutrophils and antigen-presenting cells

4. Associations of immunocompetent cells with circulating tumor cells

5. Neutrophils and natural killers

6. Tumor microenvironment and angiogenesis

7. Effect of ionizing radiation on innate immunity cells in the tumor microenvironment

8. Ionizing radiation effects modulating the tumor microenvironment

9. The effect of radiation treatment on macrophages and myeloid-derived suppressor cells of the tumor microenvironment

Conclusion

 

Keywords: peripheral blood cells, radiation exposure, carcinogenesis, innate immunity, adaptive immunity, intercellular cooperation, radiosensitivity

For citation: Kodintseva EA, Akleyev AА. The Contribution of Effector Cells of the Innate and Adaptive Immunity to the Pathogenesis of Radiation-Induced Carcinogenesis. Review (Part 2). Medical Radiology and Radiation Safety. 2025;70(5):28–35. (In Russian). DOI:10.33266/1024-6177-2025-70-5-28-35

 

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Conflict of interest. The authors declare no conflict of interest.

Financing. The research work was carried out within the framework of the state assignment of the Federal Medical and Biological Agency of Russia on the topic ‘Study of the functional state of effector cells of human antitumour immunity during the implementation of carcinogenic effects of chronic radiation exposure’ (Agreement on granting a subsidy from the federal budget for financial provision of the state assignment for public services (works) No. 388-03-2025-085 dated 24 January 2025).

Contribution. All authors confirm that their authorship meets the international ICMJE criteria. Kodintseva Е.А. – conceived and designed the study, prepared the first draft of the article, read and approved the final version before publication. Akleуev А.А. – conceived and designed the study, scientific editing, read and approved the final version before publication.

Article received: 20.05.2025. Accepted for publication: 25.06.2025.