ASSESSMENT OF QUALITATIVE CHANGES IN PERIPHERAL BLOOD CELLS IN CHILDREN – RESIDENTS OF RADIOLOGICALLY CONTAMINATED TERRITORIES IN THE LATE PERIOD AFTER THE ChNPP ACCIDENT

Objective: to establish the relationship between quantitative and qualitative parameters of peripheral blood cells (lymphocytes, neutrophilic granulocytes, monocytes, platelets) depending on the type of somatic diseases and annual internal radiation doses from 137Cs in children – residents of radiologically contaminated territories in the late period after the Chornobyl Nuclear Power Plant (ChNPP) accident. Materials and methods. There were 175 children included in the study comprising residents of radiologically contaminated territories (n = 79) aged from 4 to 18 years. Annual internal radiation doses in children from 137Cs ranged from 0.004 to 0.067 mSv. Certain blood parameters were assessed in a comparative mode in children having got the radiation doses up to 0.01 mSv and higher. The comparison group (n = 96) included children living in settlements not attributed to the radiologically contaminated ones. Incidence and type of somatic diseases and its impact on quantitative and qualitative changes in blood parameters (i.e. lymphocyte, neutrophilic granulocyte, monocyte, and platelet count) were studied. The cell size, state of nucleus, membranes and cytoplasm, signs of proliferative and degenerative processes were taken into account. Results. Incidence and type of somatic diseases in children did not depend on the annual internal radiation dose. Number of cases of monocytosis was significantly higher among the children exposed to ionizing radiation than in the comparison group (16.6 % vs. 7.3 %). There were, however, no correlation between these changes and radiation doses. Number of activated blood monocytes with cytoplasmic basophilia and residues of nucleoli in nuclei was higher in individuals with internal radiation doses > 0.01 mSv. A direct correlation between the qualitative parameters of monocytes and internal radiation doses was established (rs = 0.60; р < 0.001), as well as a direct correlation of different strength between qualitative parameters of blood cells, indicating their unidirectional pattern depending on the somatic morbid conditions. Regardless of annual internal radiation dose, there was an increase in the number of degenerative and aberrant cells vs. the comparison group (р < 0.05), which could be due to the role of non-radiation factors. Conclusions. Results of the assessment of quantitative and qualitative parameters of peripheral blood cells reflected the state of morbid conditions in children and are of a diagnostic value. The identified dose-dependent changes in monocyte lineage of hematopoiesis may be the markers of impact of long-term radionuclide incorporation with food in children living in environmentally unfavorable conditions after the ChNPP accident. Key words: annual internal radiation dose from 137Cs, children, peripheral blood, lymphocytes, neutrophilic granulocytes, monocytes, platelets, qualitative signs.

SOME ISSUES OF LIFE ACTIVITIES OF POPULATION IN THE CHORNOBYL EXCLUSION ZONE IN UKRAINE

Background. Radiation accidents at the Chornobyl Nuclear Power Plant (USSR, 1986) and Fukushima-1 (Japan, 2011) have shown that global environmental contamination is an intervention in normal human life making negative effect on population health. These accidents highlighted a number of statutory and regulatory both with medical and social problems for individuals, who returned voluntarily for permanent residence in the Chornobyl Exclusion Zone i.e. a radiation-hazardous area (they are named the «self-settlers»). Objective: generalization of experience in the settlement of normative-legal, ecological-dosimetric and medicosocial life issues of population living in the Chornobyl NPP (ChNPP) Exclusion Zone («self-settlers»). Object and methods. The chosen problem is complex, necessitating the generalization of radiation-hygienic, medical-biological, socio-economic, demographic and sociological research results obtained by the national and foreign authors. A set of theoretical research and analysis of empirical data methods on the principles of interdisciplinary interaction was used; the systematic, legal, economic, medical-biological, demographic and retrospective-dosimetric approaches of research were applied. Results. It was shown that a part of population refused to evacuate or had returned for permanent residence to the radiation-hazardous lands after the ChNPP accident. In 1986–2009 the number of «self-settlers» ranged from 150 to 2,000 in different years. In 2021 – the 101 people. Those were mainly people of working age, mostly females, single people or widows/widowers. Рrevious medical and dosimetric studies have shown that long-term residence in the Exclusion Zone affects physical and mental health of «self-settlers» and causes atypical aging, including involvement of the central nervous system. According to calculations, the average effective total radiation dose accumulated by «self-settlers» for the first 3 years was 30 % of dose for the entire post-accident period, and the dose accumulated over 20 years was 54 % of the dose accumulated over 35 years. But the effective radiation doses accumulated in different periods after the accident differ significantly in residents of different Exclusion Zone settlements. This information needs further study in terms of the «radiation dose - health status» dependence. Conclusions. The effective radiation doses accumulated in different periods after the accident differ significantly in the residents of different Exclusion Zone settlements. Тhe average effective total radiation dose accumulated by «self-settlers» for the first 3 years was 30 % of the dose for the entire post-accident period, and the dose accumulated over 20 years was 54 % of the dose accumulated over 35 years. The Scientific Council meeting of NAMS approved the NRCRM Annual Report. Key words: Chornobyl Nuclear Power Plant, Exclusion Zone, «self-settlers», radiation doses, health.

SELECTION AND TESTING OF EXPERIMENTAL MODELS OF NORMAL AND MALIGNANT HUMAN CELLS IN VITRO AND EVALUATION OF THEIR SENSITIVITY RANGE TO THE NEUTRON/CAPTURE AND PHOTON-CAPTURE AGENTS AND PHOTOSENSITIZERS

Objective: to investigate the structural and morpho-functional changes in test systems of malignant (A-549 cell line) and normal (fibroblasts of the 6th passage) human cells during incubation with gadolinium-containing photon-capture agent «Dotavist» and photosensitizer «Fotolon». Methods. The passaged (continuously interweaved) cell culture technique on normal human fibroblasts and malignant human cells; cytological, biophysical, statistical methods. Results. The cytotoxic properties of «Dotavist» gadolinium-containing photon-capturing agent and «Photolon» photosensitizer in a wide range of concentrations (5, 10, 25, 50, 100 and 200 μl/ml) were studied by the morphofunctional characteristics (growth kinetics, proliferative and mitotic activity, presence of atypical cells) in the in vitro test systems of malignant (non-small cell lung cancer cell line A-549) and normal (6th passage fibroblasts) human cells. It was found that the cytotoxic properties of «Dotavist» in test systems of malignant and normal cells are expressed under its administration in high concentrations (100 and 200 μl/ml). During incubation with «Photolon» photosensitizer the cytotoxic effect on malignant cells was determined at the lowest concentrations (5 and 10 μl/ml). Photosensitizer administration in the increasing concentrations has lead to genotoxic effects. Cytotoxic effect of photosensitizer on the normal human fibroblasts was evident in the 5-200 μl/ml concentration range. There was a moderate decrease in mitotic activity along with increasing concentration. Genotoxic properties of photosensitizer were evident at 25 μl/ml concentration and above. Conclusion. Study results of the effectiveness of neutron-capture and photon-capture technologies by the sensitivity assay in the in vitro test systems of human malignant cells (non-small cell lung cancer cell line A-549) and normal cells (transplantable human fibroblast culture, the 6th passage) to the gadolinium-containing photon-capture «Dotavist» agent and «Photolon» photosensitizer in different concentrations provide the basis for pre-clinical stage of evaluating the effectiveness of medications used in binary technologies. Key words: culture of human malignant cells, culture of human fibroblasts, neutron-capture agent, photon-capture agent, photosensitizer, proliferation, mitotic index.

HEALTH IN THE SYSTEM OF VALUES OF THE POPULATION OF THE SURVEILLANCE ZONES NUCLEAR POWER PLANTSS

Objective: to determine the place of health in the system of values of the population of the surveillance zone (SZ) of nuclear power plants (NPPs) and its importance in the perception of emergency risks (ER). Materials and methods. To determine the place of health in the value system, a survey of the able-bodied population of satellite cities of Rivne (RNPP) and South Ukrainian (SUNPP) nuclear power plants was conducted using nonrepetitive sampling, where the sampling error does not exceed 7,0 %. The motivational and behavioral component that determined health in the individual hierarchy of values of the subject according to the questionnaire Berezovskaya R. A. was studied. Statistical and mathematical methods were used in the research process. Results. The array of respondents was conditionally divided into 4 groups according to their attitude to human health. And the group where a person’s life position is focused exclusively on health is the most common – 77,0 %. Group IV, which wants to live without limiting itself, is 8,1 %. The component integrity of values-goals and valuesmeans among the urban population of the SZ of both nuclear power plants is the same: the main goal in life is health, happy family life, and as a means – perseverance, diligence and health. Goal values in groups I and IV have some differences: in the first group of respondents the main goal in life is health, and in the fourth, where a person’s life guidelines exclude any restrictions – a happy family life. Values for these populations have some differences, but in both groups health appears to be the main means to an end. There is a close correlation between the core of terminal values and the average indicators of the state of concern about the risk of emergencies. Conclusions. Identified hierarchy of values: a group of stable dominant values; average status values; group of least significant values. The values of the highest status among the values-goals are – health, happy family life and interesting work. Most respondents plan to achieve them through values such as «health», «perseverance and hard work». There is a close correlation between the core of terminal values and the average indicators of the state of concern about the risk of emergencies. Key words: health, values, population, NPP surveillance zone, perception of emergency risks.

SKIN AND SUBCUTANEOUS ADIPOSE TISSUE DAMAGE AFTER RADIATION THERAPY IN BREAST CANCER PATIENTS

The analysis of long-term researches of the pathological changes arising in soft tissues at patients with a breast cancer as a result of radical surgical treatment and adjuvant radiotherapy is carried out in work. The article shows that the standard approach to postoperative radiation therapy, which is based only on the prevalence of the primary tumor process is not always justified. Very often it leads to excessive radiation load on the patient's body and the development of local acute and chronic radiation reactions of the skin, subcutaneous tissue and other soft tissues. In this regard, the question of differentiated purpose of radiotherapy acquires special value first of all at patients with small primary prevalence of tumor process. The paper presents the results of studies to study changes in the anterior chest wall in patients with breast cancer. In relation to the conduct of adjuvant radiotherapy more often need to use the concept of personalized radiation therapy. Radical operation, post-radiation early and late pathological changes in soft tissues, disturbance of microcirculation of lymph and blood, disturbance of innervation of vessels of an upper extremity, peripheral nerves in system of a cervical and plexus plexus, leads to intensive degenerative and dystrophic changes in soft tissues of the upper. and causes morphological changes in them and further progression of reflex neurovascular and neurodystrophic disorders. Based on the data of adverse effects of radiotherapy on the skin and surrounding tissues, as well as to reduce excessive radiation exposure to the patient's body, a differentiated approach to the appointment of adjuvant radiation therapy. The Scientific Council meeting of NAMS approved the NRCRM Annual Report. Key words: breast cancer, radiation therapy, adjuvant radiation therapy, complications of radiation therapy, radiation reactions, radiation injuries.

ROLE OF GENETIC PREDISPOSITION, GENE POLYMORPHISM OF GLUTATHIONE-S-TRANSFERASE (GSTT1, GSTM1, GSTP1) AND SOME ADVERSE FACTORS IN DEVELOPMENT OF BRONCHIAL ASTHMA IN CHILDREN – RESIDENTS OF RADIOACTIVELY CONTAMINATED AREAS

Objective: to determine the influence of hereditary predisposition, polymorphism of GSTT1, GSTM1, GSTP1 genes and environmental factors on the development of bronchial asthma in children – residents of radioactively contaminated areas. Materials and methods. School-age children-residents of radioactively contaminated areas with bronchial asthma, and those without clinical signs of respiratory pathology were examined. Genetic, medical, biological and social risk factors were determined based on the study of anamnestic data and medical records. Ventilation lung capacity was assessed by the method of computer spirometry. Molecular genetic studies were carried out using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) for further analysis. Results. Molecular genetic studies of the distribution of genotypes and frequencies of polymorphic variants of the genes GSTT1, GSTM1, GSTP1 were performed in children living under long-term intake of 137Cs by food chains. It was found that in children with BA the tendency to frequency of the deletion variant of the GSTT1 and GSTM1 genes in comparison with children without bronchial and pulmonary pathology was increased. The study of distributing the GSTP1 A313G gene polymorphic variants revealed in children with BA a significant increase in the frequency of AG-genotype, compared with the data of reference group. Adverse factors that increase the risk of developing bronchoobstructive disorders and the probability of their implementation in the form of bronchial asthma in children residents of RCA have been identified. It is established that among them the leading role is played by hereditary predisposition to this disease. On the part of the child, such negative factors were unfavorable conditions of fetal development, the presence of signs of exudative-catarrhal diathesis, manifestations of allergies and frequent respiratory diseases from the first months of life. It was found that the risk of developing BA was significantly increased in children with the GSTT1 and GSTM1 gene deletion genotypes; an increased risk of developing BA in children with a combination of the GSTP1 A313G gene polymorphism with deletion polymorphism of the GSTT1 or GSTM1 gene was determined. Сonclusion. Оne of the leading mechanisms, due to which there is a realization of hereditary predisposition to bronchial asthma in children living under constant intake of radionuclides with a long half-life, is the polymorphism of certain glutathione-S-transferase genes, namely, GSTT1, GSTM1 and A313G gene deletion polymorphism and GSTP1 gene polymorphism. Key words: children, radioactively contaminated areas, risk factors, bronchial asthma, glutathione-S-transferase gene polymorphism.

SUBCLINICAL INFLAMMATION IN NON-ALCOHOLIC FATTY LIVER DISEASE AT THE REMOTE PERIOD AFTER THE CHORNOBYL ACCIDENT

Objective: to evaluate the parameters of inflammatory reaction and oxidative stress in patients with non-alcoholic fatty liver disease (NAFLD) in the remote period after the influence of the Chornobyl accident factors. Materials and methods. Eighty two patients with NAFLD who had been exposed to ionizing radiation as a result of the Chornobyl accident and have concomitant cardiovascular pathology were examined. Hematological parameters and the level of highly sensitive C-reactive protein (hsCRP) were determined, and the content of products of oxidative modification of lipids and proteins was evaluated. Results. Activation of the processes of oxidative modification of lipids and proteins was observed in most patients with NAFLD. According to the level of hsCRP, the presence of subclinical inflammation and the risk of developing complicated cardiovascular pathology was found in 58 % of patients with NAFLD. The neutrophil / lymphocyte ratio correlates positively with hsCRP and can be used as an available routine clinical marker for selection among patients with NAFLD persons with increased risk of cardiovascular complications. Conclusions. HsCRP, oxidative modification products of lipids and proteins, ESR, and leukograms should be used to assess the degree of systemic inflammation in people affected by the Chornobyl accident, suffering NAFLD with concomitant cardiovascular disease. Key words: non-alcoholic fatty liver disease, chronic subclinical inflammation, Chornobyl accident.

DENTAL CARIES INTENSITY IN CHILDREN WITH DISTURBANCES IN TOOTH FORMATION, SURVIVED AFTER THE CHORNOBYL NPP ACCIDENT

Objective: assessment of dental caries intensity in children with disturbances in tooth formation living in radiologically contaminated territories as a result of the Chornobyl NPP accident. Materials and methods. Children aged 6-14 years old (n = 1470) suffering from disturbances in tooth formation (DTF) with the residents of radiologically contaminated territories (n = 528) among them were enrolled in the study. The DTF subtypes were assayed, namely the systemic enamel hypoplasia (SEH) and molar incisor hypomineralisation (MIH). Personal radiation history was recorded. Intensity of caries and caries of surfaces in the mixed (i.e. transitional) occlusion (df+DMF, dfs+DMFS coefficients) and permanent occlusion (DMF, DMFS coefficients) was identified. Results. Caries intensity in the exposed children suffering DTF with mixed and permanent dental occlusion was significantly higher vs. either in children exposed to ionizing radiation with no DTF or in the control group (р < 0.001, р < 0.001 and р < 0.05, р < 0.001 correspondingly). The highest caries intensity of the permanent teeth was revealed in the residents of contaminated territories suffering SEH (6.95 ± 2.3) vs. cases of MIH (5.68 ± 1.97) as a result of nonsymmetrical teeth involvement. Conclusions. The highest values of df+DMF, dfs+DMFS coefficients were diagnosed in children with a mixed dental occlusion aged 6-14 years old living on territories contaminated as a result of the ChNPP accident as compared to the not exposed subjects and control group (7.2 ± 2.07 and 8.98 ± 2.4, р < 0.001). A very high intensity of caries and surface caries of permanent teeth (DMF = 6.79 ± 2.34, DMFS = 8.69 ± 2.75, р < 0.001) was established in children exposed to ionizing radiation and suffering DTF. Such a high intensity may be due to the impact of a set of negative factors including the ionizing radiation in low doses and peculiarities of economic component of social status of study subjects, namely the unbalanced diet. In case of permanent occlusion the intensity of caries and caries of tooth of in children survived after the ChNPP accident and suffering SEH was significantly (р < 0.05) higher compared to the persons suffering MIH. Key words: children, caries, disturbances in tooth formation, systemic enamel hypoplasia, molar-incisor hypomineralization, ionizing radiation, ChNPP accident.

ANXIOUSNESS AND QUALITY OF SLEEP IN CHILDREN WHO WERE IN QUARANTINE DURING THE COVID-19 PANDEMIC

Objective: to assess the level of anxiety and characterize the quality of sleep in children living in radioactively contaminated areas in comparison with children who were not affected by the Chornobyl-affected contingents that were quarantined in connection with the COVID-19 pandemic. Materials and methods. The indicators of the level of anxiety were studied using the scale of self-assessment of the level of anxiety Ch.D. Spielberger, sleep quality was assessed using a standardized questionnaire for self-completion of PSQI and 137Cs content was measured in children. The main group consisted of 96 children who were quarantined due to the COVID-19 pandemic and permanently lived in radioactively contaminated areas of Zhytomyr and Rivne regions with a soil contamination density of 137Cs from 18 kBq/m2 to 235 kBq/m2. The age of children ranged from 10 to 17 years. Among them were 33 boys and 63 girls. The comparison group consisted of 52 children of similar age, including 26 boys and 26 girls. These children lived permanently in Kyiv and were not victims of the Chornobyl disaster. Results. It was found that children who were quarantined for COVID-19 (both residents of radioactively contaminated areas and children who do not belong to the contingents affected by the Chornobyl disaster) had an increased level of reactive (RA) and personal anxiety (PA). The comparative analysis showed that children of the same sex of the main group and the comparison group did not differ in terms of PA and RA. At the same time, studies have shown that girls, both in the main group and in the comparison group, were characterized by higher levels of PA and RA than boys. It was determined that poor sleep quality was common in both children living in radioactively contaminated areas (42.71 %) and children in the comparison group (42.44 %). Among the sleep disorders in children of both observation groups, «day dysfunction» was most often detected. Conclusions. There was a direct correlation between the overall PSQI score and the level of reactive, personal anxiety and the overall PSQI score. Using regression analysis, the presence of a linear association of the level of incorporated 137Cs (Bq) with the indicator of personal anxiety of children living in radioactively contaminated territory (b = - 0.716, p < 0.001) was proved. Key words: Chornobyl disaster, COVID-19, quarantine, anxiety, sleep quality.

CLINICAL-METABOLIC AND HORMONAL RELATIONSHIPS BETWEEN PARATHYROID DISEASE AND OTHER NON-CANCEROUS ENDOCRINE DISORDERS IN THE CHORNOBYL NPP ACCIDENT SURVIVORS

Objective: to investigate the clinical, hormonal-metabolic and structural features of parathyroid injuries in survivors exposed to ionizing radiation after the Chornobyl NPP accident in adulthood and childhood, both with their connections to other non-cancerous endocrine disorders, and to establish the respective interhormonal and dysmetabolic relationships. Materials and methods. Clinical effects of ionizing radiation on the endocrine system in persons affected by the Chornobyl NPP accident (n = 224) and their descendants (n = 146), compared with the general population sample (n = 70) were the study object. All patients underwent the ultrasound thyroid and parathyroid examination. The generally recognized clinical, anthropometric (body weight, height, thigh volume, body mass index), instrumental (ultrasound examination of thyroid and parathyroid glands), laboratory (biochemical, hormonal), and statistical methods were applied. Parametric and nonparametric statistical methods were used in data processing. The value of p < 0.05 was considered a statistically significant. Results. No significant difference was found in the incidence of carbohydrate metabolic disorders in the Chornobyl NPP (ChNPP) accident consequences clean-up workers (ACCUW), evacuees from the NPP 30-km exclusion zone, residents of radiologically contaminated areas and in the control group in whom the parathyroid hyperplasia was detected. There was a significant increase in the incidence of arterial hypertension among ACCUW who had parathyroid hyperplasia (76.9%) vs. the control group (51.2%). In cases of parathyoid hyperplasia the vitamin D levels were significantly lower than without it. Vitamin D insufficiency/deficiency was found in 94% of the surveyed subjects. The average level of parathyroid hormone in blood serum was significantly higher in the ACCUW of «iodine» period with diagnosed parathyroid hyperplasia than in the control group: (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml, p < 0.05. Results of multivariative analysis indicated a strong association of vitamin 25(OH)D insufficiency/deficiency with development of thyroid disease, carbohydrate metabolic disorders, cardiovascular disease, osteopenia/osteoporosis. parathyroid ultrasound scan was at that an effective diagnostic method for primary screening for parathyroid hyperplasia and regular monitoring of the treatment efficiency. When examining children born to parents irradiated after the ChNPPA the parathyroid hyperplasia (58%) and low serum content of vitamin D (11.6 ± 3.5) nmol / l were most often found in children living on radiologically contaminated territories (RCT). A strong correlation was established between the HOMA insulin resistance index and serum content of vitamin D (r = 0.65), parathyroid hormone (r = 0.60), and free thyroxine (r = 0.68) in the group of children born to parents irradiated after the ChNPPA, having got chronic autoimmune thyroiditis, which indicated a relationship between thyroid function, impaired carbohydrate and fat metabolism and the state of parathyroids. Conclusions. No difference in the incidence of carbohydrate metabolic disorders was found in the ChNPP ACCUW, evacuees from the 30-km exclusion zone, and residents of radiologically contaminated territories in whom parathyroid hyperplasia was detected vs. the control group. Patients with parathyroid hyperplasia were found to be defi cient in vitamin D in 94% of cases, and level of latter was significantly lower than under the normal parathyroid size. There was a significant increase in the incidence of diagnosed arterial hypertension among ACCUW who had parathyroid hyperplasia vs. the control group: (76.9 ± 3.5)% vs. (51.2 ± 3.7)%. According to multivariate analysis a strong association between the vitamin 25(OH)D insufficiency/deficiency and development of thyroid disease, carbohydrate metabolic disorders, cardiovascular disease, and osteopenia/osteoporosis was established. The average level of parathyroid hormone in the blood serum of the ChNPP ACCUW of the «iodine» period with diagnosed parathyroid hyperplasia was significantly higher (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml; p <0,05) in the control group. Key words: ChNPP accident, irradiation, accident survivors, accident consequences clean-up workers, ionizing radiation, parathyroids, hyperplasia, hyperparathyroidism, thyroid.