RADIATION & RISK
Bulletin of the National Radiation and Epidemiological Registry
since 1992
About the Journal : 2025 : vol. 34, No. 4 : Comprehensive study of hematopoietic changes in non-irradiated mice kept in contact with irradiated animals

Comprehensive study of hematopoietic changes in non-irradiated mice kept in contact with irradiated animals

«Radiation and Risk», 2025, vol. 34, No. 4, pp.40-56

DOI: 10.21870/0131-3878-2025-34-4-40-56

Authors

Kogarko I.N. – Lead. Researcher, MD
Petushkova V.V. – Lead. Specialist, C. Sc., Econ. Contacts: 4 Kosygin str., Moscow, 119991, Russia. Tel: +7(495) 939-72-73; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .
Kogarko B.S. – Sen. Researcher, C. Sc., Phys.-Math.
Neyfakh E.A. – Researcher, C. Sc., Biol.
Ktitorova O.V. – Researcher, C. Sc., Biol.
Ganeev I.I. – Research Engineer. FRCCP RAS.
Selivanova E.I. – Sen. Researcher, C. Sc., Biol. A. Tsyb MRRC.
Kuzmina N.S. – Lead. Researcher, D. Sc., Biol. FRCCP RAS, VIGG RAS.
1 N.N. Semyonov Federal Research Center for Chemical Physics of RAS, Moscow
2 A. Tsyb MRRC, Obninsk
3 Vavilov Institute of General Genetics of RAS, Moscow

Abstract

Over the past decades, numerous studies have investigated the quantitative and qualitative patterns of radiobiological effects. The radiation-induced “bystander effect” at the inter-organismal level was represented by experiments obtained on hematopoietic organs and peripheral blood populations of irradiated and non-irradiated mice. It was shown that in non-irradiated mice in contact with irradiated animals (cages with a septum), on the 3-rd day after the beginning of the experiment, a significant decrease in the relative number of lymphocytes (p=0.047) was observed, accompanied by an in-crease in the percentage of eosinophils (p=0.05). The eosinophil index was also significantly in-creased in the “bystander” animals kept in cages without a septum (p=5E-5). On the 14-th day, both versions of the experiment also demonstrated a highly significant increase in the relative number of eosinophils compared to the control (p=4E-3 and p=8E-4 for the cage without septum and with the septum, respectively). At the same time, there was a tendency to an increase in the number of normo-chromatophilic erythrocytes with micronuclei (cages with a septum, p=0.09). In unexposed “by-stander” animals in the remote period (30-th day) from the beginning of the experiment, the eosinophil content continues to increase compared to the unexposed control (cages without septum, p=2E-5). On 60-th day, this group of non-irradiated mice showed a decrease in the absolute number of leuko-cytes, the percentage of lymphocytes, and an increase in the proportion of neutrophils compared to the control group (p=0,06, p=0,038, p=0,02, respectively), and on 90-th day, there was a tendency to an increase in the frequency of monocytes (p=0.05) and a significant decrease in nucleated bone marrow cells (p=0.02). On the 30-th day, the “bystanders” kept with the irradiated mice in septal cages showed a decrease in the percentage of lymphocytes (p=0.01), accompanied by an increase in the number of neutrophils (p=0,04), monocytes (p=0,04) and eosinophils (p=0.08). On 90-th day, a sig-nificant decrease in the proportion of lymphocytes (p=0,01) was revealed in these animals along with an increase in the relative number of eosinophils (p=0.02) and monocytes (p=0.05), as well as a tendency to an increase in the level of normochromatophilic erythrocytes with micronuclei compared to the control group (p=0.06). Thus, the experiment showed systemic disorders of hematopoiesis in non-irradiated mice in contact with irradiated animals, with the prevalence of long-term effects accompanied by a significant change in the percentage of leukocytes of different subpopulations.

Key words
ionizing radiation, mice, bone marrow, spleen, thymus, leukocytes, lymphocytes, erythrocytes, irradiated and non-irradiated animals, induction of radiation-induced «bystander effect», contact factor, radiobiology.

References

1. Pelevina I.I., Akleev A.V., Kogarko I.N., Petushkova V.V., Kogarko B.S., Pryakhin E.A., Neyfakh Е.А., Ktitorova O.V. Radiation-chemical effects of ionizing radiation on the organism and genotoxic disorders of the blood system. Khimicheskaya fizika – Chemical Physics, 2021, vol. 40, no. 12, pp. 48-55. (In Russian).

2. Kogarko I.N., Petushkova V.V., Kogarko B.S., Pryakhin E.A., Neyfakh E.A., Ktitorova O.V., Andreev S.S., Ganeev I.I., Kuzmina N.S., Selivanova E.I., Pelevina I.I. Investigation of the effects of ionizing radiation-induced bystander changes in the cells of the blood system of mice at the inter-organism level. Radiatsiya i risk – Radiation and Risk, 2023, vol. 32, no. 1, pp. 48-60. (In Russian).

3. Ermakov A.V., Konkova M.S., Kostyuk S.V., Veiko N.A. “DNA signaling” pathway that ensures the deve-lopment of the radiation effect of the witness in human cells. Radiatsionnaya biologiya. Radioekologiya – Radiation Biology. Radioecology, 2011, vol. 51, no. 6, pp. 651-659. (In Russian).

4. Chen S., Zhao Y., Han W., Chiu S.K., Zhu L., Wu L., Yu K.N. Rescue effects in radiobiology: unirradiated bystander cells assist irradiated cells through intercellular signal feedback. Mutat. Res., 2011, vol. 706, no. 1-2, pp. 59-64.

5. Zhang J., Xie Y., Xu Y., Pan Y., Shao C. Hydrogen sulfide contributes to hypoxia-induced radioresistance on hepatoma cells. J. Radiat. Res., 2011, vol. 52, no. 5, pp. 622-628.

6. Fedrigo C.A., Grivicich I., Schunemann D.P., Chemale I.M., dos Santos D., Jacovas T., Boschetti P.S., Jotz G.P., Braga Filho A., da Rocha A.B. Radioresistance of human glioma spheroids and expression of HSP70, p53 and EGFr. Radiat. Oncol., 2011, vol. 6, pp. 156. DOI: 10.1186/1748-717X-6-156.

7. Lam R.K.K., Fung Y.K., Han W., Li L., Chiu S.K., Cheng S.H., Yu K.N. Modulation of NF-κB in rescued irradiated cells. Radiat. Prot. Dosimetry, 2015, vol. 167, no. 1-3, pp. 37-43.

8. Mothersill C., Smith R., Wang J., Rusin A., Fernandez-Palomo C., Fazzari J., Seymour C. Biological entanglement-like effect after communication of fish prior to X-ray exposure. Dose Response, 2018, vol. 16, no. 1, pp. 1559325817750067. DOI: 10.1177/1559325817750067.

9. Reis P., Lourenço J., Carvalho F.P., Oliveira J., Malta M., Mendo S., Pereira R. RIBE at an inter-organismic level: a study on genotoxic effects in Daphnia magna exposed to waterborne uranium and a uranium mine effluent. Aquat. Toxicol., 2018, vol. 198, pp. 206-214.

10. Surinov B.P., Isaeva V.G., Dukhova N.N., Sharetsky A.N. The changes in immunomodulatory and attractive properties of mice secretions after radiation exposure or induction of the “bystander effects”. Radiatsionnaya biologiya. Radioekologiya – Radiation Biology. Radioecology, 2021, vol. 61, no. 1, pp. 5-12. (In Russian).

11. Smith R., Wang J., Seymour C., Fernandez-Palomo C., Fazzari J., Schültke E., Bräuer-Krisch E., Lais-sue J., Schroll C., Mothersill C. Homogenous and microbeam X-ray radiation induces proteomic changes in the brains of irradiated rats and in the brains of nonirradiated cage mate rats. Dose Response, 2018, vol. 16, no. 1, pp. 1559325817750068. DOI: 10.1177/1559325817750068.

12. Pelevina I.I., Kogarko I.N., Pryakhin E.A., Petushkova V.V., Kogarko B.S., Neyfakh Е.А., Andreev S.S., Ktitorova O.V., Ganeev I.I. Study of the disorders of the blood system of irradiated and unirradiated animals kept in contact. Radiatsionnaya biologiya. Radioekologiya – Radiation Biology. Radioecology, 2022, vol. 62, no. 5, pp. 477-483. (In Russian).

13. Kogarko I.N., Petushkova V.V., Kogarko B.S., Neyfakh E.A., Ktitorova O.V., Ganeev I.I., Kuzmina N.S., Selivanova E.I. Changes in the cellular composition of blood in unirradiated and irradiated mice kept in contact at the inter-organismic level. Radiatsiya i risk – Radiation and Risk, 2023, vol. 32, no. 4, pp. 147-161. (In Russian).

14. Directive 2010/63/EU of the European Parliament and of the Council of the European Union on the protection of animals used for scientific purposes. Saint Petersburg, Rus-LASA, 2012. (In Russian).

15. European Convention for the protection of vertebrate animals used for experiments or for other scientific pur-poses. Strasbourg, 1986. Available at: https://rm.coe.int/168007a6a8 (Accessed 15.05.2025). (In Russian).

16. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing. Vienna, R Core Team, 2018. Available at: https://www.R-project.org (Accessed 15.05.2025).

17. Nikitaki Z., Mavragani I.V., Laskaratou D.A., Gika V., Moskvin V.P., Theofilatos K., Vougas K., Stewart R.D., Georgakilas A.G. Systemic mechanisms and effects of ionizing radiation: a new 'old' paradigm of how the bystanders and distant can become the players. Semin. Cancer Biol., 2016, vol. 37-38, pp. 77-95.

18. Pouget J.-P., Georgakilas A.G., Ravanat J.-L. Targeted and off-target (bystander and abscopal) effects of radiation therapy: redox mechanisms and risk benefit analysis. Antioxid. Redox Signal., 2018, vol. 29, no. 15, pp. 1447-1487.

19. Lehnert B.E., Goodwin E.H., Deshpande A. Extracellular factor(s) following exposure to alpha particles can cause sister chromatid exchanges in normal human cells. Cancer Res., 1997, vol. 57, no. 11, pp. 2164-2171.

20. Hei T.K., Zhou H., Ivanov V.N., Hong M., Lieberman H.B., Brenner D.J., Amundson S.A., Geard C.R. Mechanism of radiation-induced bystander effects: a unifying model. J. Pharm. Pharmacol., 2008, vol. 60, no. 8, pp. 943-950.

Full-text article (in Russian)