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.

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.

EXPRESSION OF BIOLOGICAL MARKERS INDUCED BY IONIZING RADIATION AT THE LATE PERIOD AFTER EXPOSURE IN A WIDE RANGE OF DOSES. / EKSPRESIIa RADIATsIINO-INDUKOVANYKh BIOLOGIChNYKh MARKERIV U VIDDALENOMU PERIODI PISLIa OPROMINENNIa U ShYROKOMU INTERVALI DOZ.

OBJECTIVE: To study radiation induced biological markers of the late period after exposure. SUBJECTS AND METHODS: A study was performed in 235 Chornobyl accident male clean-up workers exposed in 1986-1987 (doses of external exposure: (M ± SD: 419.48 ± 654.60; range 0.10-3,500 mSv); age 58,34 ± 6,57 years. Controlgroup included 45 non-exposed subjects (mean age: 50.60 ± 5.37 (M ± SD). Gene expression was performed by RT-PCR on 7900HT Analyzer using TLDA for BCL2, CDKN2A, CLSTN2, GSTM1, IFNG, IL1B, MCF2L, SERPINB9, STAT3, TERF1, TERF2,TERT, TNF, TP53, CCND1 genes. Relative telomere length (RTL) was analysed by flow-FISH; immune cell subsets,γ-H2AÐ¥ and CyclinD1 expression by flow cytometry. RESULTS: A statistically significant and dose-dependent decrease in expression of the BCL2, SERPINB9, CDKN2A, andSTAT3 genes was demonstrated in parallel to a dose-dependent overexpression of MCF2L and upregulation of TP53 (upto 100 mSv). IL1B expression was the highest in exposed to doses from 0.1 to 100 mSv with a negative correlationbetween at IL1B expression and CD19+3-, CD3-HLA-DR+, CD4+8- cell counts and CD4+/CD8+ ratio. Hyperexpression ofTNF gene in doses above 100 mSv to 1,000 mSv was shown, and in higher doses a combination of TNF downregula-tion with increase in IFNG gene expression were demonstrated with correlations with numbers of CD3+16+56+ andCD25+ lymphocytes and inhibition of expression CLSTN2. An increased expression of γ-H2AÐ¥ and Cyclin D1 corre-lated to radiation dose, telomere shortening to age and concommittant pathology. CONCLUSIONS: Cellular immunity, gene expression, telomere length, intracellular protein parameters are shown to beamong perspective biological markers at a late period after radiation exposure.

Impact of chronic blood viral infection on lymphocyte telomere length in Chornobyl clean-up workers in a remote period after radiation exposure. / VPLYV KhRONIChNOÏ VIRUSNOÏ INFEKTsIÏ NA DOVZhYNU TELOMER LIMFOTsYTIV PERYFERYChNOÏ KROVI UChASNYKIV LIKVIDATsIÏ AVARIÏ NA ChAES U VIDDALENOMU PERIODI PISLIa OPROMINENNIa.

OBJECTIVE: To assess whether telomere length in lymphocytes of Chornobyl clean up workers at a late period 30 years after the exposure to ionizing radiation is influenced by a chronic blood viral infection and to determine role of viral carriage in cellular senescence. PATIENTS AND METHODS: Study group included 70 Chornobyl cleanup male workers 30 years after exposure {doses of external exposure (602.67 ± 114.19) mSv (M ± m); age (59.75 ± 0.82) yrs}. Relative telomere length (RTL) was analysed by fluorescence in situ hybridization and flow cytometry, immune cell subsets by standard combinations of monoclonal antibodies (CD45/14, CD3/19, CD4/8, CD3/HLADR, CD3/16/56, TCRγδ) and flow cytometry; antiviral immunity was performed determining the chronic phase antibodies to viruses: Hepatitis C (HCV), Cytomegalovirus (CMV), Toxoplasma gondii (TOX), Herpes simplex (HSV) and Epstein Barr virus (EBV VCA IgG and EBV NA IgG). The object of the study was peripheral blood (PB) of clean up workers. RESULTS: RTL changes were associated at the group level with the carrier state of the viral infection. RTL shortening was demonstrated as a significant difference between the groups (M ± SD) (HCV negative 15.27 ± 3.35, HCV posi tive 13.09 ± 3.05, p < 0.08, n = 12/52) or as a tendency (CMV negative 15.99 ± 5.41, CMV positive 14.86 ± 3.46 (M ± SD), p < 0.57, n = 11/53; HSV negative 17.01 ± 1.35, HSV positive 14.79 ± 3.80, p < 0.33, n = 13/51; TOX neg ative 15.94 ± 3.41, TOX positive 14.30 ± 3.81(M ± SD), p < 0.23, n = 27/37). These unidirectional changes can be associated with premature early cell aging of immune cells. To the contrary the significant RTL elongation was demonstrated in the group of EBV NA chronic carriers (EBV NA negative 11.25 ± 3.02 (M ± SD), EBV NA positive 16.15 ± 3.08 (M ± SD), p < 0.001, n = 15/49). CONCLUSION: The study confirmed the assumption on a relationship existing between the telomere length, chronic viral infection and late effects in immune cells. The changes of telomeres length on the background of immune dys function may be a sign of cellular aging, and concomitant chronic blood viral infection such as Hepatitis C, Epstein Barr viruses carriage could form a background for an error prone DNA reparation system as a factor of accumulation of pathological conditions, including malignant transformation.