Vol 68, No 1 (2023)
Radiation Biology
Cytogenetic Analysis of the Cell Line of Multipotent Human Mesenchymal Stromal Cells during Long-Term Cultivation after Exposure to X-Ray Radiation at Low and Medium Doses
Abstract
Purpose: To evaluate the frequency and spectrum of chromosome aberrations under X-Ray exposure at doses of 80, 250, and 1000 mGy in a human multipotent mesenchymal stromal cell (MMSC) cell line during long-term cultivation.
Material and methods: MMSCs were isolated from human gingival mucosa by an enzymatic method and cultured in a serum-free medium. The presence of surface antigens was determined using the method of flow cytometry. The ability of the cell line to differentiate in the osteogenic, adipogenic, and chondrogenic directions was studied using induction media. Authentication was performed by genotyping of polymorphic STR loci, cytogenetic analysis was performed by multicolor fluorescent in situ hybridization (mFISH). Irradiation was carried out on an X-ray biological unit RUB RUST-M1 (Russia) at a dose rate of 40 mGy/min, a voltage of 100 kV, and a current of 0.8 mA.
Results: At the first passage after irradiation, a statistically significant increase in the frequency of non-clonal CA compared with the control was recorded at a dose of 80, but not 250 and 1000 mGy. At the late stages of cultivation, the average frequency of breaks per chromosome in the group of non-irradiated cells did not differ from the values obtained after irradiation at doses of 80, 250, and 1000 mGy (p > 0.05). However, in MMSCs irradiated at a dose of 80 mGy, damage occurred more often in pairs of chromosomes 6 and 10, and at a dose of 1000 mGy, in a pair of chromosomes 9. A single irradiation of MMSCs in vitro did not affect the growth and progression of MMSCs characteristic of the studied primary cell line, of clonal cells with chromosome translocations and monosomy X, but led to an increase in the representation of a clone with tetrasomy 8. The total number of random clones with chromosome translocations that arose de novo increased after irradiation at a dose of 1000 mGy.
Conclusion: Minor fluctuations in the proportion of cells with non-clonal CA, depending on the dose received in the early stages after irradiation (passage 1–4), disappeared at the later stages of cultivation (passage 8–14). There were no differences in mean frequencies between irradiated and non-irradiated MMSCs, but after irradiation, damage to some chromosomes could occur more frequently than others. A single X-ray irradiation of MMSCs can promote the growth and progression of primary pathological cytogenetic clones, regardless of the dose received, as well as an increase in the total number of de novo cell clones with chromosomal translocations that have arisen. A single X-ray irradiation of MMSCs can promote the growth and progression of primary pathological cytogenetic clones, regardless of the dose received, as well as an increase in the total number of de novo cell clones with chromosomal translocations that have arisen.
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Mechanisms of Antitumor Activity of Low Doses of Radiation Associated with Activation of Cells' Defense System
Abstract
Background: The effects of ionizing radiation (IR) involve a highly orchestrated series of events in cells, including DNA damage and repair, cell death, and changes in the level of proliferation associated with the stage of the cell cycle. A large number of existing studies in literature have examined the activity of genes and their regulators in mammalian cells in response to high doses of ionizing radiation. Although there are many studies, the research in effect of low doses of ionizing radiation remains limited. Though much progress has been made in understanding the basic principles of effects of low doses radiation on individual components of biological systems, less is known about how low doses affect target molecules and regulate the cellular networks (e.g., activation of the immune system, genes and their regulators in the phenomenon of hormesis, the formation of an adaptive response). These observations determined the purpose of the work: to investigate the activity of genes and non-coding RNAs (long non-coding RNAs and microRNAs) in various organs of mice with transplanted Lewis carcinoma after low doses radiation.
Material and methods: 24 female mice C57Bl/6 were transplanted subcutaneously with Lewis carcinoma cells (105 cells in 0.2 ml of Hanks’ solution). Total 4-fold X-ray irradiation with an interval of 4 days at a dose of 0.075 Gy (0.85 Gy/min) was performed on the RUST M1 from 6 days after transplantation; the tumor size was measured daily. The mice were divided into the following groups: biocontrol, biocontrol+irradiation, tumor and tumor+irradiation. On the 19th day from the beginning of the experiment, the mice were euthanized. The expression profiles of mRNA genes, long non-coding RNAs and microRNAs controlling the response to radiation were determined in the bone marrow, thymus, spleen and tumor of mice.
Results: Fractionated low doses irradiation of mice with transplanted Lewis carcinoma caused a growth decrease of implanted tumour cells compared to the similar group without irradiation. At the same time, there was an activation of oncosuppressors, and a decrease in the activity of oncogenes in the thymus and spleen of mice with tumor and irradiation. In the tumor group, without irradiation, the number of activated oncogenes prevailed over the number of inactivated ones.
Conclusion: Thus, the low doses radiation exposure led to the activation of antitumor immunity in mice, which emerged in slowing tumor growth in animals and was represented in the induction of oncosuppressors and inhibition of oncogenes expression.
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Radiation Safety
The Concept of the Digital Twin of the Radiation and Nuclear Facilities' Worker
Abstract
Purpose: Analysis of the possibilities of a predictive model for assessing the risks of pathology of the cardiovascular, cerebrovascular systems and psychophysiological state in workers of radiation and nuclear hazardous enterprises and industries as part of the development of the concept of a digital twin.
Material and methods: The study involved employees of one of the leading radiation and nuclear hazardous enterprises, who underwent periodic medical examinations at comprehensive medical health center of the A.I. Burnazyan Federal Medical and Biological Center in September–October 2022. In total 154 patients (115 men and 39 women) were questioned, examined, and analyzed medical records. Diagnostic criteria for risk factors and other pathological conditions and diseases that increase the likelihood of developing chronic non-communicable diseases were evaluated both in accordance with the orders of the Ministry of Health and using the AI-HIPPOCRAT digital prognostic model developed by the Computer Science and Management Federal Research Center.
Results: In accordance with the criteria specified in the orders of the Ministry of Health, it was revealed that high or very high risks of developing diseases such as heart attack, stroke, hypertension and depression are observed in 120 people (77.9 %), and according to the analysis in the AI-HIPPOCRAT system, these risks occur in 131 people (85.1 %).
Conclusion: As a result of the study, the capabilities of the AI-HIPPOCRATE system were analyzed and the following recommendations were given for its use by workers of radiation and nuclear hazardous enterprises and industries: to integrate the AI-HIPPOCRAT system into the medical information system used at the enterprise; to divide the presented risk factors into three groups: manageable (on which the doctor or patient can influence), conditionally manageable (which can be influenced by the use of drugs) and uncontrollable, which the doctor and the patient cannot manage (for example, gender, age, etc.); to raise the threshold for setting the risk of a particular disease to “high and above”.
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Distribution of Radiocarbon in the Environment under Normal Conditions of Operating of Kurskaya Nuclear Power Plant
Abstract
Introduction: 14C is one of the fifteen radionuclides that account for at least 99 % of the radiation dose to the critical group of the population from NPP emission sources. The continuous growth of the total capacity of operating NPPs leads to a significant increase in the amount of 14С emitted into the environment during NPP operation. Efficient capture and disposal of 14C, which has a half-life of 5760 years, is a very laborious undertaking. At the same time, due to the high mobility of this radionuclide, local foci of contamination with 14C can appear both near the NPP at a distance of 1–2 km from its ventilation pipe, and in soil and plants located at a distance of 20–30 km from the NPP due to the transfer of air masses. Therefore, the control of the formation of 14C during the operation of nuclear power plants, its content in emissions and discharges of nuclear power plants, as well as distribution in the environment is an urgent problem today.
Purpose: Analysis of the environmental pollution due to emissions and discharges of radiocarbon from the Kurskaya nuclear power plant.
Material and methods: During the research, a method being developed by specialists of the Laboratory for Radiation Safety of Personnel was used to determine the specific activity of 14C in soil and vegetation. To explore the 14C content in the air, the method of bubbling air through a TASC-HT-HTO-C-14 flow meter-sampler (Overhoff technology, USA) and the method of air conditioning through a Ballu BDH-15L air dryer (Ballu, Russia) were used. To prepare counting samples from selected soil and food samples, a method based on the combustion of selected samples in a Pyrolyser-6 Trio catalytic decomposition system was used. All prepared counting samples, including samples from surface water and biosubstrate of the personnel of the Kursk NPP and the population, were measured by liquid scintillation spectrometry on a Tri-Carb 3180 TR/SL alpha, beta spectrometer.
Results: On the basis of an integrated approach to assessing the content of 14C in air, water, soil and food, an analysis of the formation of environmental pollution due to emissions and discharges 14C from the Kurskaya NPP was carried out.
Conclusions: An increased content of the 14C radionuclide in soil samples, food products and vegetation in the area of the Kursk NPP with RBMK-1000 nuclear reactors is shown, both in comparison with the content of natural 14C and NPPs operating BN-600,800 and VVER-1000 nuclear reactors. The necessity of taking into account radiocarbon emissions from NPPs into the environment in the problem of optimizing the radiation protection of the population under the conditions of normal operation of NPPs is confirmed.
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Radiation Medicine
Features of the Dynamics of the Peripheral Blood Lymphocytes during the First Week in Combined Radiation-Mechanical Lesions
Abstract
For a long time, the attention of researchers studying combined radiation-mechanical injuries (CRMI) has been focused on the study of individual syndromes: mechanical trauma and acute radiation syndrome. To diagnose and assess the severity of each syndrome, tests used for isolated injuries are recommended. However, the results of tests based on counting the number of different peripheral blood cells in an initially healthy person and in an injured patient who has experienced severe bleeding will be different. Accordingly, the assessment of the severity of developing acute radiation disease these patients will differ.
The possibility of predicting the severity of developing radiation injury in CRMI using a lymphatic test during the first week after exposure is also being evaluated. In this report, based on the literature data, the dynamics of the absolute number of lymphocytes in patients with multiple mechanical injuries is considered.
The results of numerous clinical and experimental studies indicate that severe and multiple injuries, starting from the first hours and during the first week of observation, are characterized by instability of the number of lymphocytes in peripheral blood with significant absolute lymphopenia on the first day. It is shown that the depth of lymphopenia and the rate of recovery of the number of lymphocytes to normal values depends on the severity of the mechanical injury. In addition, the deepening of lymphopenia is also caused by urgent medical measures that are standard in the provision of medical care for severe trauma with blood loss: massive infusion therapy and the appointment of corticosteroids.
Thus, the use of a lymphocytic test in CRMI to assess the radiation dose without taking into account the significance of the trauma suffered will lead to a false prognosis of the degree of developing acute radiation damage, as well as to the lack of differentiation between the effects of radiation and non-radiation factors, and, consequently, to errors in patient management tactics.
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Toxic Pneumosclerosis as a Consequence of Chronic Plutonium Exposure
Abstract
Purpose: To assess toxic pneumosclerosis caused by inhalation intake of plutonium aerosols in a patient who worked in contact with plutonium at the Mayak Production Association from 1948–1954.
Material and methods: Patient Sh., born in 1924, higher education, at the age of 24, began working as a chemical engineer at MPO Mayak from 1948 to 1954 under conditions of increased occupational hazard of ionizing radiation (exposure to gamma rays and ingestion of plutonium aerosols). During her work, she received 389, 624 R: (1950 ‒ 83, 57; 1951 ‒ 187, 29; 1952 ‒ 70, 24; 1953 ‒ 48, 14). Carrying plutonium.
Results: А clinical description of toxic pneumosclerosis of a severe degree of a progressive course, caused by the intake of mainly transportable plutonium aerosols against the background of a combined effect of external relatively uniform gamma radiation, is given. The carriage of plutonium and its removal from the body were established and confirmed. For diagnostic and therapeutic purposes, the patient underwent pentacin inhalations in 2 stages for 3 days. The excretion of plutonium-239 in the urine increased to a maximum of 940 units / min ‒ 1150 units / min (06.04.1957‒06.06.1957) and 464 units / min (06.14.1957), in feces ‒ 308 units / min ‒ 252 units / min (06.07.1957‒ 06.11.1957) and 236 units / min (18.06.1957). The assessment of the amount and alpha activity of the received in the lungs, liver, bones, and other organs was carried out according to the biophysical study of the organs of the corpse of the patient Sh.
Conclusion: The clinical picture of the patient was determined by toxic plutonium pneumosclerosis of a severe degree of progressive course as a consequence of chronic exposure to plutonium. Hypoxia (hypoxemic and tissue). Pulmonary heart. Focal pneumonia. Upex lungs. Violation of the vasomotor and respiratory centers. Moderate oppression of hematopoiesis and asthenic syndrome as a consequence of chronic radiation sickness II degree. The disease progressed with damage to the main critical organs (lungs, liver, bones). The patient died from heart failure, which developed as a result of pneumosclerosis with symptoms of asphyxia.
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Radiation Epidemiology
Comparative Assessment of the Absorbed Doses Resulted from Occupational Exposure and Computed Tomography
Abstract
A comparative assessment of the absorbed doses resulted from computed tomography (CT) examinations, and the dose resulted from occupational external gamma exposure of the “Mayak” workers was carried out. The patients’ diagnostic radiation dose was reconstructed using Monte-Carlo simulation on a population of 58 virtual adult phantoms across 13 CT protocol categories. Archival records of CT examinations of patients were used for the dose reconstruction. Information on technical parameters of scanning was extracted from DICOM files. The study sample has been linked to the Mayak worker register database to identify persons who had professional contact with ionizing radiation. Annual occupational dose records for the Mayak workers were obtained from the Dose-2013 dosimetry system.
In this study, information on 212 patients was collected from 303 records. Among them, 42 Mayak employees were identified, including 24 persons who had non-zero dose of external gamma radiation, and 16 persons with internal alpha radiation dose due to occupational intake of 239Pu. Individual doses absorbed in the organs resulted from exposure to computed tomography and occupational activities has been compared.
The results showed significant variability of the absorbed organ dose depending on the area of CT examination. The brain and lens were subjected to the highest radiation exposure during head CT. The average absorbed dose in brain was 24.5 mGy per single examination (the maximum brain dose accumulated over the entire study period was 82.3 mGy), and 27.7 mGy for the lens of the eye (the maximum lens dose reached 92.9 mGy).
Relevant comparison of the absorbed dose of diagnostic and occupational exposure, accumulated during one year, has been performed. The average estimate of cumulative radiation dose absorbed in the organs during computed tomography was an order of magnitude lower than the one from occupational external gamma exposure of Mayak personnel, except brain dose. Annual CT dose equivalent of external gamma radiation was 2.82.
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Radiation Therapy
Threshold Thermal Dose of Local Hyperthermia in Thermoradiation Therapy of Tumors
Abstract
The review analyzes the damaging, radio- and chemosensitizing effects of various temperature regimes of hyperthermia on normal and tumor cells in the experiment and on the results of thermoradiation therapy for cancer patients. According to the criteria of minimum, average and maximum temperatures, as well as the cumulative equivalent time for heating 90 % of the tumor volume at 43 °C (CEM43T90), lower threshold thermal doses have been determined that significantly affect the immediate results of thermoradiation therapy. The maximum allowable temperatures for normal skin and with postoperative scars or radiation fibrosis have been established.
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Radiation Therapy and Pregnancy (Literature Review)
Abstract
The possibility of radiation therapy during pregnancy remains a subject of discussion, in most cases, specialists try to avoid the use of radiation therapy in a pregnant woman. Currently, there is insufficient data confirming the safety of intrauterine radiation even with the use of modern methods of radiation therapy.
The purpose of this literature review is to summarize current clinical data on the appropriateness of the use and clinical results of the use of radiation therapy for the treatment of the most commonly diagnosed tumors in pregnant women.
Based on the literature data, it can be said that the possibility of using radiation therapy in the treatment of oncological diseases in pregnant women depends on the localization of the tumor, gestational age, the estimated total focal dose, the size of the irradiation field, the distance from the irradiation field to the fetus, the preferences of the patient.
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Nuclear Medicine
Method of Experts' Quality Evaluation of the PET Images of the Patients
Abstract
Purpose: To develop the method of experts’ quality evaluation of the PET images as an additional quality control method for accurate, comparable, and reproducible PET diagnostics results, and to conduct image quality evaluation in different PET departments used this method.
Material and methods: 60 PET images (without CT) of the patients who underwent whole body PET/CT with 18F-FDG were collected from 12 PET/CT scanners in 9 PET departments. Experts’ quality evaluation was conducted with questioning of the experts. Each expert evaluated the image quality by five-point scale and filled out the special form which include three image quality criteria: image clarity, artefacts, and general image quality. There were 28 experts from 8 different PET departments who have work experience in radiology from 1 to 32 years. The results of experts’ quality evaluation of the PET images were examined for correlations with parameters of acquisition and reconstruction protocols, examination methods. The results were also examined for dependance of subjective factors such as work experience and work conditions of experts. The minimum required number of experts were defined. The results were analyzed used statistical methods.
Results: The PET images obtained by 8 PET/CT scanners had mean quality value more than 4 points (good quality). PET/CT scanners, which had the lowest quality value, have the obsolete or unusual settings and reconstruction parameters. The correlations between experts’ quality evaluation of the PET images and acquisition parameters (acquisition time per bed, multiplication of injected activity and acquisition time per bed), and examination methods (injected activity and uptake time) were established. The results of experts’ quality evaluation of the PET images were dependent on work experience and work conditions of experts.
Conclusion: The method of experts’ quality evaluation of the PET images of the patients based on the questioning of the experts working in PET was developed and demonstrated in the current study. The results showed this method has the potential to compare the PET images obtained by different acquisition and reconstruction protocols, and it can be applied during the optimization of examination method and for the determination of obsolete and unusual settings of PET/CT. Experts’ evaluation of the PET images should include the opinion of at least six experts with different work experience in PET from several PET departments.
Key words: positron emission tomography, experts’ evaluation, diagnostics quality, image quality control
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Single-Photon Emission Computed Tomography with 99mTc-1-Thio-D-glucose in Evaluation of the Effectiveness and Prediction of the Results of Treatment of Lymphoproliferative Diseases
Abstract
Purpose: Study of 99mTc-1-thio-D-glucose (99mTc-TG) SPECT using fore possibility to assess the effectiveness of therapy and predict the results of lymphomas treatment.
Material and methods: We analyzed 99mTc-TG SPECT data of 30 people with malignant lymphomas: before treatment (SPECT1), after two courses (SPECT2) and after completion of chemotherapy (SPECT3).
Results: By the results of SPECT2 analyzing, a complete metabolic response after two courses of chemotherapy (SPECT2–) was observed in 15 patients (50 %). In 15 patients, after 2 cycles of chemotherapy, a partial metabolic response (12 people) or no metabolic response (3 people) was established. These patients constituted the SPECT2+ group.
After completion of chemotherapy, a complete metabolic response (SPECT3–) was diagnosed in 21 (70 %) patients. This effect was obtained in 15 (100 %) patients with SPECT2– and in 6 patients (40 %) with SPECT2+. Of the 15 patients in the SPECT2+ group, 9 (60 %) patients after completion of chemotherapy were diagnosed with a partial metabolic response (6 people) or metabolic progression (3 people).
By two-year follow-up of patients, show that remission was observed in 23 (77 %) patients (complete remission in 15 people, uncertain complete remission in 8 patients). The relapse group consisted of 7 (23 %) cases, while 4 patients had a relapse of the disease, and 3 had progression. In SPECT2+ group, relapse of the disease was observed in 6 (40 %) cases, and remission in 9 (60 %) patients. While in SPECT2– group 1 (7 %) person relapse was diagnosed and 14 (93 %) were in remission (p<0.05).
Conclusion: 99mTc-TG SPECT makes it possible to evaluate the results of lymphomas treatment with high efficiency. The presence of a complete metabolic response of the tumor after two courses of therapy indicates a high level of disease-free survival.
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Radiation Physics, Technique and Dosimetry
Tritium Dosimetry at the Cellular Level
Abstract
Introduction
1. Tritium radioisotope and its energy spectrum
2. Methods for calculating doses from radiation of radionuclides
2.1 General equation for absorbed dose rate
2.2 Absorbed dose rate versus average energy
2.3 Formulas for calculating dose and S-values from radiation of radionuclides
2.4 Method of dose point nuclei
2.5 MIRD effective stopping power method
2.6 Geometric factor
3. Analysis of S-value calculations by various methods
3.1 Values of the CSDA range at low initial electron energies
3.2 Comparison of S-value calculations for low energy electrons
3.3 Comparison of tritium S-value calculations
4. Evaluation of S-value calculations in the absence of spherical symmetry
Conclusion
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New books
Review of the book by Nikolai Alekseevich Pomerantsev "Chernobyl: Pilots and Aviation Medics. How it was..." (Historical-Documentary Scientific Edition)
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