Urals Research Center for Radiation Medicine

The pituitary gland exposure can lead to increase the risk of hormone-dependent cancers, such as breast cancer. The pituitary gland is located in the pituitary fossa of the sphenoid bone and can be exposed due to bone-seeking radionuclides such as 90Sr. The Commission on Radiological Protection does not distinguish the pituitary gland as a separate organ for absorbed dose calculating from incorporated radionuclides. In this regard, an urgent task is to create a dosimetric model that simulates the geometry of the source-tissues – the bones of the skull, and the target-tissue – the pituitary gland and adjacent tissues. This model will allow us to calculate the dose factors converting the activity concentration of radionuclide in the bone to the absorbed dose rate in the pituitary gland. To develop such a model, it is necessary to provide a systematic review of data on the size of the pituitary gland and surrounding tissues. Objective: to evaluate the morphometric characteristics necessary for constructing a computational dosimetric phantom of the pituitary gland and its adjacent tissues for people of the following age groups: newborn, 1-year-old, 5-year-old, 10-year-old, 15-year-old, adults. Materials and methods: The dosimetric model is supposed to include anatomical structures located within 1.5 cm around the pituitary gland. Therefore, the characteristics of the following tissues were evaluated based on published data: part of the brain, content of the sphenoid sinus, vessels around pituitary gland, pituitary gland, the sphenoid bone. Results and Discussion: The characteristics of the simulated objects were evaluated for all age groups, for the sella turcica they ranged from 3.4-13.3 mm, and for the pituitary gland – 3.8-13.6 mm. These values are based on studies of ~5,000 people. The size of the vascular sinuses is estimated at 1-1.7 mm, the thickness of the membranes of the pituitary gland is 0.57 mm. The thickness of the cortical bone was 0.75 mm, and the bone volume to total bone volume ratio was 39 %. Conclusion: The results of this work will be used for creating of three-dimensional computational dosimetric phantoms of the pituitary gland and its surrounding tissues for different age groups.

Introduction. Epidemiological studies suggest that ionizing radiation increases the risk of developing neurodegenerative diseases long after exposure; however, there is a notable lack of longitudinal studies and experimental research into establishing causal relationships between radiation dose and potential neurodegenerative effects. Objective. The work investigates early and long-term alterations in sensorimotor parameters characterizing coordination in laboratory animals subjected to a range of doses of fractionated gamma irradiation at a young age. Materials and methods. Experiments were carried out on mice of both sexes ( n = 400) of the C57Bl/6 strain. Five observation groups were formed: two control groups and three groups with different radiation exposure levels, each made up of 80 individuals (40 males and 40 females). The animals underwent total external gamma irradiation during their first month of life at cumulative doses of 0.1 Gy, 1 Gy, and 5 Gy, with each dose divided into 20 fractions. The control groups of non-irradiated mice included: a group of intact animals serving as biological control ( n = 80) and a sham-irradiation placebo group ( n = 80). Evaluation of motor function is an effective tool for assessing symptoms of neurodegenerative diseases in animals. Coordination in irradiated and control animals was assessed using the tapered beam walking test at the ages of 1, 6, 12, and 18 months. Data were analyzed using Microsoft Excel and the R programming language. Results. Sex and age were shown to influence sensorimotor parameters characterizing motor coordination (better in females, worsens with age in animals of both sexes), while no significant effect of the stress factor associated with animal irradiation was found on the studied parameters. A comparison of sex- and age-standardized sensorimotor parameters between irradiated animals and non-irradiated control mice revealed dose-dependent alterations. A deteriorated in motor coordination in the long term in mice exposed to gamma irradiation at a cumulative dose of 5 Gy manifested itself by a more than 1.5-fold increase in the number of errors compared to non-irradiated animals ( t = 6.7; p << 0.001). Conversely, irradiation at a cumulative dose of 0.1 Gy produced an opposite effect: both in the early and long-term periods, the speed of mouse movement along the tapered beam increased relative to the non-irradiated control (walking time decreased by an average of 20% ( p < 0.001) at any age), while in the early period, the number of errors also decreased ( t = 2.36; p = 0.02), indicating an improvement in coordination ability. Conclusions. Fractionated gamma irradiation at a young age induced dose-dependent alterations in sensorimotor function in animals: irradiation at a cumulative dose of 0.1 Gy resulted in improved coordination both in the early and long-term periods post-exposure; whereas irradiation at a cumulative dose of 5 Gy led to signs of impaired motor coordination in the long term, at 18 months of age.

In the middle of the 20th century residents of the Ural region were affected by chronic radiation exposure in a wide dose range due to the release of liquid radioactive waste into the Techa River. The objective of the study was to investigate the dynamics of the frequency of unstable chromosome exchanges in chronically exposed residents of the Techa riverside settlements. Materials and Methods: The study covers the period from 1970s through 2019. The analysis is based on the published research describing the results of cytogenetic examination, as well as on the retrospective study of the cytogenetic database data. Nine groups of examined individuals were formed by periods of examination: five groups of exposed people and four comparison groups. To obtain the preparations, T-lymphocytes were cultivated to the metaphase stage and hypotonically treated; the metaphase plates were fixed, and the chromosome preparations were prepared. Results and Discussion: Results of the assessment showed a decrease in frequency of dicentrics and unstable chromosome exchanges over the period from 1970 through 2019. Most significant decline in the number of chromosome aberrations was observed starting from 1993, i.e. 40–50 years after the onset of exposure. Dicentrics are statistically significantly more frequent in the group of exposed people relative to the comparison group in the periods 1970-1993 (23-43 years after the onset of exposure), and 1993-1996 (46-49 years after the onset of exposure), as well as in the period from 2012 through 2019 (65-72 years after the onset of exposure). Conclusion: At present, frequency of dicentrics in exposed people remains statistically significantly increased relative to the comparison group members. State-of-the-art equipment and use of special software packages in the work of cytogeneticists made it possible to increase the number of analyzed cells in more than 3 times. It increased considerably the probability of chromosome aberration detection both in exposed and unexposed individuals.

Currently, computational phantoms that simulate skeletal tissues are used in active red bone marrow (AM) internal dosimetry. Up-to-date reference computational phantoms recommended by the ICRP are based on the analysis of CT-images of cadavers. Such phantoms have significant disadvantages. One disadvantage is that the assessment of uncertainty due to the population variability of skeleton dimensions and microstructure results from the limited availability of autopsy material. Another disadvantage is the simplified modelling of cortical layer and bone microarchitecture. A method of stochastic parametric skeletal dosimetry modelling of the bone structures – SPSD modelling – has been developed as an alternative to the ICRP reference phantoms. In the framework of this approach, skeletal phantom parameters are evaluated based on extensively reviewed results of published measurements of real bones. The SPSD approach allows for the assessment of both population-average values and their variability. SPSD-phantoms of the skeleton are modelled in voxel representation. They consist of smaller phantoms of the bone sites – segments – described by simple geometric shapes with uniform microarchitecture parameters. Such segmentation makes it possible to account for non-homogeneous skeletal microarchitecture and to model the bone structure with the required voxel resolution to elaborate suitable skeletal phantoms. The current study presents the parameters of the SPSD skeletal phantoms for the following age-groups: newborn, 1-year-old, 5-year-old, 10-year-old, 15-year-old (male and female), and adult (male and female). This skeletal phantom can be used for dosimetry as an alternative to available reference phantoms for bone-seeking radionuclides. The above-mentioned age- and sex-specific skeletal phantoms are comprised of 289 unique segments. The characteristics of the SPSD phantoms do not contradict published data and are in good agreement with the measurement results of real bones.

Currently, computational phantoms that simulate skeletal tissues are used in active red bone marrow (AM) internal dosimetry. Up-to-date reference computational phantoms recommended by the ICRP are based on the analysis of CT-images of cadavers. Such phantoms have significant disadvantages. One disadvantage is that the assessment of uncertainty due to the population variability of skeleton dimensions and microstructure results from the limited availability of autopsy material. Another disadvantage is the simplified modelling of cortical layer and bone microarchitecture. A method of stochastic parametric skeletal dosimetry modelling of the bone structures - SPSD modelling - has been developed as an alternative to the ICRP reference phantoms. In the framework of this approach, skeletal phantom parameters are evaluated based on extensively reviewed results of published measurements of real bones. The SPSD approach allows for the assessment of both population-average values and their variability. SPSD-phantoms of the skeleton are modelled in voxel representation. They consist of smaller phantoms of the bone sites - segments - described by simple geometric shapes with uniform microarchitecture parameters. Such segmentation makes it possible to account for non-homogeneous skeletal microarchitecture and to model the bone structure with the required voxel resolution to elaborate suitable skeletal phantoms. The current study presents the parameters of the SPSD skeletal phantoms for the following age-groups: newborn, 1-year-old, 5-year-old, 10-year-old, 15-year-old (male and female), and adult (male and female). This skeletal phantom can be used for dosimetry as an alternative to available reference phantoms for bone-seeking radionuclides. The above-mentioned age- and sex-specific skeletal phantoms are comprised of 289 unique segments. The characteristics of the SPSD phantoms do not contradict published data and are in good agreement with the measurement results of real bones.

BACKGROUND: Chronic radiation exposure due to residence in areas contaminated with radionuclides remains a pressing concern globally, as it increases the risk of leukemia, solid malignancies, and other diseases. According to current understanding, many human pathologies are underpinned by somatic mosaic mutagenesis, particularly involving sex chromosomes. The X chromosome plays a critical role in immune function and autoimmune pathogenesis, and X chromosome aneuploidy is linked to development of various somatic disorders. Prior cytogenetic studies of radiation-exposed populations in the Southern Urals revealed increased X chromosome involvement in micronuclei formation, warranting further investigation into X chromosome aberrations. AIM: To assess intra- and interchromosomal aberrations involving the X chromosome in peripheral blood T lymphocytes in women with chronic radiation exposure during long-term follow-up. METHODS: This pilot study included five women exposed to chronic radiation in the Southern Urals (mean age: 74.0 ± 0.8 years; mean cumulative red bone marrow dose: 1.35 ± 0.30 Gy). A comparison group consisted of five women (mean age: 66.3 ± 1.2 years; mean red bone marrow dose: 0.010 ± 0.006 Gy; range: 0–0.03 Gy) who lived under similar socioeconomic conditions and had received less than 70 mGy of total red bone marrow exposure during follow-up. X chromosome aberrations were analyzed using multicolor banding (mBAND). Aberration frequency was calculated per genome equivalent, adjusted for donor age. The frequency of cells with X chromosome aneuploidy was also assessed. RESULTS: The frequency of X chromosome aberrations was higher in irradiated women compared to the comparison group (0.100 ± 0.036 vs 0.019 ± 0.011; U = 3, p = 0.0476). In irradiated women, a greater variety of aberration types was noted, including a ring chromosome, an isochromosome, and a chromosome presumably formed as a result of chromothripsis. The mean frequencies of X chromosome aneuploidy in irradiated women did not differ significantly from those in the comparison group (p = 0.4); however, interindividual variation may exist. CONCLUSION: The findings may indicate a more intense mutational process in individuals chronically exposed to radiation. The study of X chromosome aberrations in peripheral blood T lymphocytes of women chronically exposed to radiation in the Southern Urals is promising and should be continued.

Breast cancer (BC) is a multifactorial disease that is characterized by various genetic and epigenetic changes that occur due to the effect of various factors including that of environmental etiological agents. The obtained scientific data speak volumes for epigenetic dysregulation in BC pathogenesis. Out of all epigenetic markers, various microRNA regulating a wide spectrum of biological processes in a cell could be viewed as one of the predictors of potential risk. Understanding the functional role of these molecules will provide valuable information about the complex molecular mechanisms underlying the appearance and development of BC. This review summarizes currently existing publicly available data on aberrant expression of miR-125b, miR-181a, and miR-16 in case of various cancer localizations; analyzes their role in BC pathogenesis; presents an annotation of the target-genes; and evaluates the repression potential of microRNA and their diagnostic significance in case of BC. An analysis of changes in miRNA expression during radiation exposure was conducted. Interest in examining specific miRNAs is due to the results of long-term monitoring of the health of people living in radioactively contaminated areas of the Southern Urals, as well as data on the expression profiles of miR-125b, miR-181a, and miR-16 over the long term in exposed people.

This article analyzes the kinematics of a crank mechanism and evaluates the feasibility of organizing the operating process using two-phase fuel injection in a V-engine with trailing connecting rods and identical piston strokes. The advantages and disadvantages of two main connecting rod designs are highlighted, allowing us to evaluate the characteristics of the additional bending moment and the factors influencing its formation. Two main connecting rod designs are considered. The first has an angle between the longitudinal axes of the main connecting rod and its trailing rod equal to 60, while the second has an angle of 67 with a cylinder V angle of 60. A comparative kinematic analysis of the main connecting rod design, performed using the first and second designs, as part of the crank mechanism of a V-2 engine, allowed us to determine the angle between the trailing connecting rod axis and the side cylinder axis, which characterizes the occurrence of an additional bending moment. Several fundamental principles are defined for implementing a two-phase fuel injection system using the first design of the main connecting rod, as well as the injection angles of the pilot and main fuel portions, with the goal of creating an identical operating process to that achieved with the second design of the main connecting rod. The conditions for the fuel injection moment under the influence of negative factors acting on the main connecting rod are graphically presented, as well as the relevance of a two-phase fuel injection system. It is concluded that implementing a two-phase fuel injection system to the cylinders while maintaining uniform piston stroke and minimizing the negative impact of additional bending moment is a promising approach to improving the technical level of V-shaped engines with attached connecting rods.

Every year, more and more data demonstrate that microRNA expression levels can be changed significantly after acute radiation exposure, and microRNAs themselves play an important role in the cellular response to ionizing radiation. However, regulation of microRNA expression after chronic radiation exposure within the low and middle dose range is poorly studied. In the present study, the expression of mature miR-29a, miR-30c, and miR-150 microRNAs in whole blood from 81 individuals in the long-term period after chronic low dose-rate radiation exposure was analyzed by real-time PCR method. The mean age of the studied people was 72 years, and the accumulated radiation doses in red bone marrow (RBM), thymus, and peripheral lymphoid organs ranged from 2.13 to 1867.55 mGy and from 0.18 to 488.79 mGy, respectively. More than 70 years after the onset of radiation exposure, a statistically significant dose-dependent decrease in miR-30c microRNA expression was found in exposed individuals in RBM, thymus, and peripheral lymphoid organs.