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

Participating countries and international organizations:

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

Issues addressed and main goals of research:

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

The research and development will include:

• 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 tissues of different parts of animals' central nervous system after exposure to radiations of different LET.

• Research on the induction and molecular nature of different types of gene and structural mutations in mammalian and lower eukaryote cells depending on the radiation dose and LET, repair status, oxidative stress development, and genetic stability mechanisms.

• Research on the formation of complex chromosomal aberrations in normal and tumor cells of humans and laboratory animals. Evaluation of long-term consequences of exposure to radiations of different LET.

• Research on behavioral reaction disorders and pathomorphological changes in different structures of the brain, spinal cord, and critical organs and systems of irradiated laboratory animals. Conducting a search for new radioprotective drugs.

• Research on radiation-induced effects in microglia, oligodendrocytes and their precursors, and in the myelin sheath after exposure to densely ionizing radiation.

• Research on the mechanisms of the action of Ara-C and other radiosensitizers for the irradiation of different normal and tumor cell cultures and mice with transplanted tumors.

• Development of an hierarchy of mathematical models of radiation-induced biological effects that would describe the development of radiation-induced pathologies at different organization levels (from molecules to cell populations) and at different times (acute and long-term consequences).

• Improvement of accelerator-based radiobiological experiment procedures. Calculation of shieldings for new nuclear physics facilities; evaluation of the radiation conditions and development of radiation safety systems for them. Participation in the creation and tests of nuclear planetary science instruments.

Expected results in the current year:

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

• 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.

• 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.

• To continue studying the formation and repair kinetics of clustered DNA DSBs in neuron precursor cell nuclei and mature neurons and in glial cells of the mammalian central nervous system (CNS) after accelerated heavy charged particle exposure — using the cell subpopulation markers NeuN, doublecortin, GFAP, BrdU, and calbindin.

• 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.

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

• To continue studying DNA DSB formation and repair in mammalian CNS neurons after γ-ray and accelerated heavy ion exposure.

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

• To study the radiosensitivity of probiotic yeast strains.

• To continue research on the influence of respiratory impairment caused by mitochondrial DNA damage on yeast cells' sensitivity to radiation's lethal and mutagenic effects.

• To map the mutations that decrease yeast cells' radiosensitivity and study the radioprotection mechanism.

• To study the influence of yeast phosphatase HAP1 inactivation on the radiosensitivity and genetic stability of the nuclear and mitochondrial genomes.

• To analyze structural and chromosomal damage in radiation-induced mutants at different times after irradiation of a mammalian cell culture.

• To perform metaphase analysis of long-term chromosomal damage after irradiation of Macaca mulatta monkeys' head with accelerated krypton ions.

• To continue an mFISH analysis of complex aberration induction in human normal (lymphocytes) and tumor (Cal51 breast carcinoma) cells by photons, accelerated protons, and accelerated nitrogen ions.

• To continue mFISH analysis of chromosomal aberrations induced in human peripheral blood lymphocytes by different types of radiation used in cancer therapy.

• To continue mFISH karyotyping and analysis of structural and numerical chromosomal aberrations in different lines of human stem cells cultivated in vitro.

• To continue premature chromatin condensation analysis of the induction of chromatin breaks in human normal (lymphocytes) and tumor (Cal51 breast carcinoma) cells by γ-rays and accelerated protons and ions at different times after exposure.

• To study the secretion of the inflammatory cytokines TNF alpha, IL-1, IL-6, and MCP-1 in mouse brain homogenates at different times after mouse head irradiation with Bragg peak protons.

• To evaluate the level of the myelin basic protein (MBP) in mouse brain homogenates at different times after mouse head irradiation with Bragg peak protons.

• To continue studying the effect of cytosine arabinoside (Ara-C) on the survival of different mammalian and human normal and tumor cell lines by the criteria of clone formation and apoptosis after exposure to accelerated protons and γ-rays.

• 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 γ-rays — under normal conditions and in the presence of Ara-C (±HU).

• To continue studying DNA DSB formation in different parts of rodent CNS after in vivo irradiation with accelerated protons and γ-rays without radiomodifiers and in the presence of Ara-C (±HU).

• To continue studying modifications of small laboratory animals' behavioral reactions after heavy charged particle (HCP) exposure in the presence of AraC.

• To evaluate the pathological changes in different cell populations of the brain and the possibility of arresting such damage by the neuroprotective drug Cerebrolysin.

• To continue studying morphological and functional changes in the CNS of SD rats and CD-1 mice after accelerated proton exposure.

• To continue research on pathogenesis in different mammalian tissues and organs after HCP exposure.

• To study the long-term effects of the morphological changes in the rat CNS after accelerated proton exposure.

• To study changes in the lipid composition of the mouse and rat brain after accelerated proton exposure.

• To continue mathematical modeling of DNA damage formation and repair after irradiation of normal and tumor cells with HCP of different energies.

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

• To perform mathematical modeling of the growth of a tumor cell population after ionizing radiation exposure in the presence of metal nanoparticles.

• To continue molecular dynamics modeling of impairments in the structure and functioning of mutant and oxidized forms of neuron proteins.

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

• To continue the design, testing, and calibration of nuclear planetary science instruments using fast neuron generators at the LRB's stand.

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

• To participate in the design and fabrication of the SODIB biological long-range ion irradiation station at the Nuclotron's radiobiological channel.

• To develop a project of a galactic cosmic ray simulator at the SODIB biological long-range ion irradiation station at the Nuclotron's radiobiological channel.

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

Collaboration