Research on the Biological Effects
of Heavy Charged Particles of Different Energies

Participating countries and international organizations:

Armenia, Belarus, Bulgaria, Czech Republic, Cuba, Germany, Italy, Mongolia, Poland, Romania, Russia, Serbia, Slovakia, Uzbekistan, Vietnam.

Issues addressed and main goals of research:

Theoretical and experimental research on the biological effects of heavy charged particles of different energies at JINR's basic facilities.

Research and development will include:

1. Research on the mechanisms of the development of DNA molecular damage and its repair in cultures of human and mammalian normal and tumor cells and in histological sections of normal and tumor tissues of animals exposed to radiations of different LET.

2. Research on the induction and molecular nature of gene and structural mutations and genetic stability mechanisms in higher and lower eukaryote cells after exposure to ionizing radiations of different quality.

3. Research on the formation of complex chromosomal aberrations in human and mammalian normal and tumor cells after exposure to radiations of different LET.

4. Research on behavioral reaction disorders and pathomorphological changes in central nervous system (CNS) structures of irradiated laboratory animals.

5. Research on neurodegenerative changes in different CNS structures after exposure to ionizing radiations of different quality.

6. Research on the molecular and cellular mechanisms of the action of cytosine arabinoside (Ara-C) in normal and tumor cells in combination with different modifiers of reparative DNA synthesis after proton beam and photon exposure.

7. Mathematical modeling of acute and long-term biological effects at different levels of biological organization (from the molecular to tissue one) after exposure to radiations of different quality.

8. Improvement of methods of physical and dosimetric monitoring of charged particle beams of different energies for radiobiological experiments. Calculation of shieldings for new nuclear physics facilities. Participation in designing and testing nuclear planetary science instruments.

Expected results in the current year:

1. To continue the analysis of clustered DNA double-strand break (DSB) formation and repair in human skin fibroblast nuclei and radioresistant U87 glioblastoma tumor cells after accelerated heavy charged particle exposure.

2. To continue the analysis of the formation and structure of complex clustered DNA damage by immunocytochemical staining of the repair proteins γH2AX, 53BP1, OGG1, and XRCC1 in human fibroblast nuclei after accelerated heavy ion exposure.

3. To continue comparative analysis of the proportion of different DNA DSB repair pathways in human fibroblasts by immunocytochemical staining of the repair proteins RAD51 (HR) and DNA PKcs (NHEJ) after exposure to radiations of different quality.

4. To continue experiments to study the expression of the genes encoding the repair proteins (RAD51, DNAPKcs, NBS1, MRE11, etc.) in human skin fibroblasts after accelerated heavy charged particle exposure.

5. To continue studying apoptosis induction in human skin fibroblasts and mammalian CNS neurons after accelerated heavy charged particle exposure.

6. To continue studying clustered DNA DSB formation and repair in mammalian CNS cells after photon and accelerated heavy ion exposure.

7. To continue research on the induction of structural rearrangements in yeast cells by radiations of different LET.

8. To continue research on the influence of mitochondrial DNA damage on yeast cell radiosensitivity and mutagenesis.

9. To continue the analysis of chromosomal damage in radiation-induced mutants at different times after irradiation of a mammalian cell culture.

10. To perform metaphase and mFISH analysis of chromosomal aberrations in peripheral blood lymphocytes of Macaca mulatta monkeys induced by ionizing radiations with different physical characteristics.

11. To continue mFISH analysis of complex aberrations in human normal and tumor cells induced by ionizing radiations with different physical characteristics.

12. To study the radiation-induced secretion of the inflammatory cytokines TNF alpha, IL-1, IL-6, and MCP-1 in mouse brain homogenates in the long term after mouse head irradiation with accelerated protons.

13. To evaluate the level of the myelin basic protein (MBP) in mouse brain homogenates in the long term after mouse head irradiation with accelerated protons.

14. To continue studying the formation and elimination of γH2AX/53BP1 foci in cultures of U87 glioblastoma and B16 melanoma cells after exposure to Bragg peak protons and photons in the presence of Ara-C in combination with different modifiers of reparative DNA synthesis.

15. To continue studying DNA DSB formation in different parts of rodent CNS after in vivo irradiation with protons and photons in the presence of Ara-C in combination with different modifiers of reparative DNA synthesis.

16. To analyze and evaluate morphological changes and apoptosis (by TUNEL staining) in the liver, brain, and kidneys of mature rats after the combined use of AraC and proton radiation.

17. To analyze the neuroprotective effect of Cerebrolysin after proton irradiation of small laboratory animals.

18. To continue the study of behavioral, morphological, and functional disorders in rodents at different times after exposure to photon and proton beams.

19. To apply computer vision algorithms to biological data processing, in histology, and in behavioral experiments.

20. To continue mathematical modeling of DNA damage formation and repair kinetics after irradiation of normal and tumor cells with heavy charged particles of different energies.

21. To continue mathematical modeling of the dynamics of a tumor cell population after ionizing radiation exposure in the presence of DNA synthesis inhibitors.

22. To continue molecular dynamics modeling of structure and function impairments in synaptic receptor proteins.

23. To continue mathematical modeling of radiation-induced neurogenesis and gliogenesis impairments and neuroinflammatory processes in CNS structures.

24. To perform mathematical modeling of chromosomal aberration induction in mammalian and human cells by ionizing radiations with different characteristics.

25. In cooperation with the RAS Institute of Space Research, to continue testing the tagged proton method at the DLNP Phasotron.

26. To ensure the conduction of radiobiological experiments at JINR's accelerators.

27. To participate in the design and fabrication of the SIMBO station at ARIADNA applied beams of the NICA complex.

28. To develop a project of a space radiation simulator for Nuclotron's applied beams.

29. To measure the radiation environment (neutron fields) around the NICA booster during commissioning.

Collaboration