THE INFLUENCE OF THE WAR FACTOR ON AGE CHANGES IN THE SUBPOPULATION STRUCTURE OF LEUCOCYTES AS A COMPONENT OF INFLAMMAGING IN THE GROUPS OF MILITARY PERSONNEL AND CLEAN-UP WORKERS OF THE CHORNOBYL ACCIDENT. / ВПЛИВ ФАКТОРА ВІЙНИ НА ВІКОВІ ЗМІНИ СУБПОПУЛЯЦІЙНОЇ СТРУКТУРИ ЛЕЙКОЦИТІВ ЯК СКЛАДОВОЇ ІНФЛАМЕЙДЖИНГУ У ГРУПАХ ВІЙСЬКОВОСЛУЖБОВЦІВ ТА УЧАСНИКІВ ЛІКВІДАЦІЇ НАСЛІДКІВ АВАРІЇ НА ЧАЕС.

OBJECTIVE: to evaluate the subpopulation structure of peripheral blood leukocytes as a component of inflammaging in the servicemen of the Armed Forces of Ukraine and clean-up workers of the accident at the Chornobyl nuclear power plant. MATERIALS AND METHODS: Three hundred ninety-seven males aged 30-82 (54.99 ± 8.85) years examined. Among them: clean-up workers of the accident at the Chornobyl nuclear power plant, aged 54-64 (59.95 ± 1.88) years, who were examined before the beginning and during the Russian military invasion of Ukraine; 24 civilians of the control group, aged 50-77 (58.87 ± 7.18) years and 15 persons of the age control group, aged 42-49 (46.00 ± 2.26) years, who examined before the war has started; the comparison group-W - 27 civilians (age: 51-82 (65.44 ± 9.13)) and the age control group-W - 14 civilians (age: 31-49 (40.64 ± 5.59)) who examined after the war has started; 73 servicemen of the Armed Forces of Ukraine aged 30-49 (42.20 ± 5.35) years and 54 servicemen aged 50-59 (54.07 ± 2.86) years. The subpopulation distribution of peripheral blood leukocytes was analyzed using flow cytometry. RESULTS: A decrease in the relative number of CD45+ 14- granulocytes, CD3+ HLA-DR+ T-lymphocytes, and CD3-57+ NK against the background of an increase in the number of CD45+ 14+ monocytes, CD3-HLA-DR+ B-lymphocytes found in the majority of people in the examination groups, the study of which conducted after the beginning of the war, CD4+ T-lymphocytes and CD3+ 57+ NKT. The relative number of CD45+ 14- granulocytes increased against the background of a decrease in CD45+ 14- lymphocytes was noted in clean-up workers who were examined before the war started.About 30% of civilians over 50 years of age who were examined before the war started had a decrease in CD19+ B- lymphocytes, CD4+ and CD8+ T-lymphocytes, CD3-57+ NK, CD3+ 57+ NKT, and the CD4+ / CD8+ ratio. Conducted correlation analysis revealed a weak to moderate inverse correlation between the relative number of CD19+ B-lymphocytes and age in civilians, regardless of when they were examined, and the servicemen of the Armed Forces of Ukraine.Inverse correlations of HLA-DR+ B-lymphocytes, CD45+ 14+ monocytes, CD4+ T-lymphocytes, CD4+ / CD8+ ratio, and CD3-57+ NK and CD3+ 57+ NKT with age were noted in civilians who were examined after the war has started. A direct correlation between CD3+ 57+ NKT and age was found in the servicemen of the Armed Forces of Ukraine. CONCLUSIONS: The immunological profile of both clean-up workers in the Chornobyl nuclear power plant and the servicemen of the Armed Forces of Ukraine or civilians was similar compared to the group with reference indicators. Anintergroup study revealed changes in the subpopulation distribution of peripheral blood leukocytes, which may be associated with both aging and changes in living conditions during military operations. Specific changes in cellular immunity can either tip the balance towards inflammaging or indicate already existing immunopathologicalreactions.

COMORBID PATHOLOGY IN FATAL CASES DUE TO CORONAVIRUS DISEASE (COVID-19) IN VICTIMS OF THE CHORNOBYL NPP ACCIDENT. / КОМОРБІДНА ПАТОЛОГІЯ ПРИ ЛЕТАЛЬНИХ ВИПАДКАХ ВНАСЛІДОК КОРОНАВІРУСНОЇ ХВОРОБИ (COVID-19) У ПОСТРАЖДАЛИХ ВНАСЛІДОК АВАРІЇ НА ЧОРНОБИЛЬСЬКІЙ АЕС.

INTRODUCTION: The victims of the Chornobyl accident, as well as whole population of Ukraine, have become the object of the COVID-19 pandemic in today's conditions. As of 01.01.2020, 108,898 victims had documented permanent disability (persons with disabilities) and, as a rule, suffered from 4-6 types of non-tumor chronic diseases of internal organs, primarily the circulatory system, as well as oncological and endocrine pathology, that significantly affect the course of COVID-19 in a severe scenario and contribute to death. This determines the relevance of the issue of the impact of comorbid pathology in fatal cases due to coronavirus disease (COVID-19) in victims of the Chornobyl accident.The Objective of the study was to study the nature and significance of comorbid pathology in the victims of the Chernobyl accident who died from COVID-19.Design, object and methods of the study - a retrospective non-randomized, comparative comprehensive analysis of the materials of 134 medical expert cases of male clean-up workers of the Chornobyl accident who died from COVID-19 in 2020-2022 during the pandemic was carried out. The analysis of the materials of expert cases included the study of clinically significant and morphologically confirmed pathological processes. The source of the data was the materials of the Central Interdepartmental Expert Commission of the Ministry of Health of Ukraine on the establishment of causal relationship of diseases, disability and death with the action of ionizing radiation and other harmful factors as a result of the Chernobyl accident. RESULTS: In the structure of comorbid pathology in the clean-up workers of the Chornobyl accident who died due to COVID-19 during 2020-2022, diseases of the circulatory system dominate, which occurred in 86.57% of cases of consideration of medical expert cases. AH complicated the course and contributed to the development of fatal consequences in 52.24% of cases, ChIHD - in 34.32% of cases. The consequences of acute vascular events in the form of post-infarction cardiosclerosis in patients with ChIHD contributed to death in COVID-19 in 29 (21.64%) cases.Cerebrovascular pathology represented by cerebral atherosclerosis was detected in 76 (56.72%) cases of death from COVID-19. Acute vascular cerebral events in the cerebral basin (ischemic and hemorrhagic strokes) contributed to fatal outcomes in 19 (14.18%) cases. The presence and course of diabetes mellitus also had a significant impact on the course and fatal mortality of COVID-19 - 24.63% (33 cases). Chronic respiratory diseases (COPD) influenced the course of COVID-19 and contributed to death in 6.72% (9) of cases, nephrological pathology (ChTIN) - in 2.98% (4) of cases, peptic ulcer disease of the duedenum - in 2.24% (3) of cases. More than half of the clean-up workers of the Chornobyl NPP accident who died due to COVID-19 had more than two severe chronic diseases of the comorbid component and their complications. CONCLUSIONS: Сlean-up workers of the Chornobyl accident who died from COVID-19 had another severe comorbid chronic disease, or several diseases that influenced the course of coronavirus disease and each other and contributed to the development of fatal consequences. Death from COVID-19 is much more common in clean-up workers of the Chornobyl accident suffering from severe disabling non-oncological diseases of the cardiovascular system (arterial hypertension, coronary heart disease), cerebrovascular diseases with consequences of acute vascular events, as well as diabetes mellitus. Victims of the Chornobyl catastrophe, especially clean-up workers of the Chornobyl NPP accident, are at special risk for severe coronavirus disease and death from COVID-19.

STATUS OF THE CELLULAR IMMUNITY IN CLEAN-UP WORKERS OF THE CHORNOBYL ACCIDENT AND PATIENTS WITH CANCER OF THE MOUTH CAVITY, ORAL AND LARYNGEAL PART OF THE PHARYNX. / STAN KLITYNNOGO IMUNITETU V UChASNYKIV LIKVIDATsIÏ NASLIDKIV AVARIÏ NA ChAES TA KhVORYKh NA ZLOIaKISNI NOVOUTVORENNIa POROZhNYNY ROTA, ROTOVOÏ TA GORTANNOÏ ChASTYN GLOTKY.

OBJECTIVE: to establish cellular immunity in clean-up workers of the Chornobyl accident compared to patients with malignant neoplasms of the oral cavity, oral and laryngeal parts of the pharynx according to the subpopulation organization of peripheral blood leukocytes. MATERIALS AND METHODS: We examined 112 males, age (56,92 ± 6,17) years (M ± SD), including 26 male clean-up workers exposed at the radiation dose 10-500 mSv; 20 male clean-up workers exposed at the dose range 504-990mSv; 33 patients with malignant neoplasms of the oral cavity, oral and laryngeal parts of the pharynx and 33 non-exposed subjects of the control group. Immune cell subsets analysis was performed by the expression of differential and activation antigens of peripheral blood leukocytes using flow cytometry. RESULTS: In assessing each group's cellular immunity, there was a decrease in the number of CD19+ B-lymphocytes, CD3+ HLA-DR+ T- and CD3- HLA-DR+ B-lymphocytes, CD3- 16+ 56+ natural killer cells, combined with an increase in the number of CD8+ T-lymphocytes. An increase in the relative number of CD4+ CD8+ T-lymphocytes was determined in clean-up workers (D < 500 mSv) and cancer patients. An increase in the number of CD8+ T-lymphocytes and a decrease in the number of CD4+ T-lymphocytes were observed in clean-up workers (D > 500 mSv), as well as in cancer patients. In addition, a decrease of monocytes, CD3+ 16+ 56+ , and CD3+ TCRαß+ T-lymphocytes was determined in patients with oncological pathology. CONCLUSIONS: The obtained results show the unidirectionality of changes in cellular immunity in the participants of the liquidation of the consequences of the accident at the Chornobyl nuclear power plant and patients with the investigated oncological pathology, which indicates the formation of persistent violations of antitumor protection in the participants of the liquidation of the consequences of the accident as the basis of oncogenesis. Determining changes in the number of lymphocytes, monocytes, granulocytes, CD4+ T-lymphocytes, CD4+ CD8+ immature T-lymphocytes, the immunoregulatory ratio CD4+ / CD8+, CD3+TCRαß+ T-lymphocytes and CD3+ 16+ 56+ CTL can have an additional effect on the effectiveness antitumor protection and the probability of oncogenesis risk in immunocompromised individuals.

СHARACTERISTICS OF CYCLIN D1-MEDIATED REGULATION OF CELL CYCLE OF PERIPHERAL BLOOD LIMPHOCYTES OF CHORNOBYL CLEAN-UP WORKERS AND PERSONS WITH MALIGNANT NEOPLASMS OF THE ORAL CAVITY, OROPHARYNX AND LARYNGOPHARYNX. / KhARAKTERYSTYKA TsYKLIN D1-OPOSEREDKOVANOÏ REGULIaTsIÏ KLITYNNOGO TsYKLU LIMFOTsYTIV PERYFERYChNOÏ KROVI UChASNYKIV LIKVIDATsIÏ NASLIDKIV AVARIÏ NA ChAES TA OSIB, KhVORYKh NA ZLOIaKISNI NOVOUTVORENNIa POROZhNYNY ROTA, ROTOVOÏ TA GORTANNOÏ ChASTYN GLOTKY.

OBJECTIVE: to explore proliferative potential of peripheral blood lymphocytes of Chornobyl clean-up workers and persons with malignant neoplasms of the oral cavity, oropharynx and laryngopharynx by level of expression of cyclin D1 and quantitative parameters of cell cycle. MATERIALS AND METHODS: A total of 294 men aged (58.47 ± 7.32) were surveyed, 215 of them were Chornobyl clean"up workers (1986-1987), exposed at the dose range 10.43-3623.31 mSv; 49 persons of the control group and 30persons with malignant neoplasms of the oral cavity, oropharynx and laryngopharynx at III, IVА and IVВ stages ofthe disease. The analysis of parameters of cell cycle and proliferative activity of peripheral blood (PB) lymphocyteswas performed using the flow cytometry. The evaluation of distribution of cells by G0/G1, S, G2/M cell cycle phaseswas done in vivo and in in vitro. Proliferative potential was analyzed by level of expression of cytoplasmic protein ofcyclin D1. RESULTS: Proliferative potential of PB lymphocytes of Chornobyl clean"up workers and persons with malignant neo"plasms of the oral cavity, oropharynx and laryngopharynx was assessed. An increase in the level of spontaneousсyclin D1 expression and disturbance of сyclin D1-dependent regulation of cell cycle of PB lymphocytes after mito"gen activation were determined in the Chornobyl clean-up workers. An increase in pool of cells in the S" and G2/M"phases of cell cycle was detected, which characterizes high proliferative potential of PB lymphocytes. These changesare most pronounced in the subgroup of persons with a radiation dose of D > 500 mSv, and in persons with oncolo"gical pathology. CONCLUSIONS: A positive linear dependence has been established between the radiation dose and the number of cellsin the S"phase of cell cycle in the subgroup of Chornobyl clean"up workers with a radiation dose of D > 500 mSv. The detected changes of cyclin D1-dependent regulation of cell cycle and proliferative status of lymphocytes depend on the radiation dose, can be a manifestation of genome instability and be a cause for risks of oncogenesis, in a remote period after radiation exposure.

CHANGES OF CYCLIN D1-DEPENDENT REGULATION OF CELL CYCLE IN PERIPHERAL BLOOD LYMPHOCYTES OF CHORNOBYL CLEAN-UP WORKERS AT A REMOTE PERIOD AFTER RADIATION EXPOSURE. / PORUShENNIa TsYKLIN D1-ZALEZhNOÏ REGULIaTsIÏ KLITYNNOGO TsYKLU LIMFOTsYTIV PERYFERYChNOÏ KROVI UChASNYKIV LIKVIDATsIÏ NASLIDKIV AVARIÏ NA ChAES U VIDDALENOMU PERIODI PISLIa OPROMINENNIa.

OBJECTIVE: To study proliferative potential of peripheral blood lymphocytes of Chornobyl clean-up workers by levelof expression of cyclin D1 and quantitative parameters of cell cycle at a remote period after radiation exposure. MATERIALS AND METHODS: The research subject was the peripheral blood lymphocytes (PB) of Chornobyl clean-upworkers 30-33 years after radiation exposure. A total of 207 men were surveyed, 164 of them were clean-up workers exposed in the dose range 10.43-3623.31 mSv and 43 persons of the control group. Analysis of proliferationpotential (cell cycle initiation) and cyclin D1 expression in PB lymphocytes were performed in vitro by a micro methodof whole blood leukocytes culture with phytohemagglutinine-P (PHA). Sample preparation was performed by a standard immunofluorescent assay for intracellular proteins using the FITC labelled Mouse Anti-Human Cyclin D1Antibody Set. Cell distribution by cell cycle phases studied by propidium iodide DNA staining and analysis onFACSCalibur laser flow cytometer in histogram mode with separation of G0/G1-, S- and G2/M-regions and Sub-G0/G1-region (apoptotic cells). RESULTS AND CONCLUSIONS: An increase in the level of spontaneous сyclin D1 expression and disturbance of сyclinD1-dependent regulation of cell cycle of PB lymphocytes after mitogen activation were determined in a remote period after radiation exposure. An increase in the level of cyclin D1 expression was accompanied by increase in pool ofcells in the S- and G2/M-phases of cell cycle which characterizes the high proliferative potential of PB lymphocytes.Mitogen-induced delay of cell cycle of lymphocytes in G1/S check point and reduction of S-phase was revealed.These changes are a manifestation of genomic instability caused by the effect of radiation and depend on the radiation dose. The results confirm the hypothesis about the significance of levels of cyclin D1 expression, as a criterion for manifestations of genome instability and risks of oncogenesis in a remote period after irradiation.

CHANGES IN GENE EXPRESSION ASSOCIATED WITH NON-CANCER EFFECTS OF THE CHORNOBYL CLEAN-UP WORKERS IN THE REMOTE PERIOD AFTER EXPOSURE. / ZMINY GENNOÏ EKSPRESIÏ, ASOTsIIOVANI Z NEPUKhLYNNYMY EFEKTAMY VIDDALENOGO PERIODU PISLIa OPROMINENNIa V UChASNYKIV LIKVIDATsIÏ NASLIDKIV AVARIÏ NA ChAES.

OBJECTIVE: to establish the connection of radiation-induced changes in gene expression with the realized pathology of the broncho-pulmonary and cardiovascular systems in Chornobyl clean-up workers. MATERIALS AND METHODS: We examined 314 male Chornobyl clean-up workers (main group; age (58.94 ± 6.82) years(M ± SD); min 33, max 79 years; radiation dose (411.82 ± 625.41) mSv (M ± SD); min 1.74, max 3600 mSv) with various nosological forms of cardiovascular and broncho-pulmonary pathology (BPP) and 50 subjects of the controlgroup: age (50.50 ± 5.73) years (M ± SD); min 41, max 67 years. The relative level of BCL2, CDKN2A, CLSTN2, GSTM1,IFNG, IL1B, MCF2L, SERPINB9, STAT3, TERF1, TERF2, TERT, TNF, TP53, CCND1, CSF2, VEGFA genes expression was determined inperipheral blood leukocytes by real-time PCR (7900 HT Fast Real-Time PCR System (Applied Biosystems, USA)). The«gene-disease¼ association was determined on statistical models stratified separately for each disease and gene.Logistic regression was used to calculate the odds ratio. RESULTS: Increased GSTM1 gene expression and no changes in angiogenesis-related VEGFA gene expression werefound in the main group of patients with coronary heart disease (CHD). It was established overexpression of TP53,VEGF and IFNG genes in the group of patients with arterial hypertension (AH). At combination of these diseases anincrease of expression of СSF2, TERF1, TERF2 genes was established. The detected changes demonstrate an activationof the antioxidative defense system in patients with CHD, while AH is associated with the expression of genes ofangiogenesis and immune inflammation. It was shown an increase in the expression of genes associated with apoptosis and kinase activity (BCL2, CLSTN2, CDKN2), immune inflammation (CSF2, IL1B, TNF) in Chornobyl clean-upworkers with BPP. Expression of TP53 and GSTM1 (gene, associated with the glutathione system) was significantlyupregulated in the group of individuals with chronic bronchitis, whereas in patients with chronic obstructive pulmonary disease, no increase was detected; the expression of SERPINB9 and MCF2L genes was downregulated. CONCLUSIONS: Changes in the expression of genes, associated with the development of somatic pathology in theremote period after irradiation, in particular the genes of the immune response and inflammatory reactions CSF2,IFNG, IL1B, TNF; expression of genes that regulate cell proliferation, aging and apoptosis TP53, BCL2, MCF2L, CDKN2A,SERPINB9, TERF1, TERF2, TERT; genes that regulate cell adhesion and angiogenesis CLSTN2, VEGF.