Background. Cytogenetic damage (СD) in lymphocytes induced by low doses (up to 0.1 Sv) of ionizing radiation (IR) is the main cytogenetic sign of individual radiosensitivity of the human body. In addition to DNA repair and cell death, which affect the formation of СD and its elimination, IR effects on the cell can be manifested through changes in proliferation of cells with unrepaired DNA damage. The system of cyclins and cyclin-dependent kinases (CDK), which provide coordination of mitotic events during passage of a cell through the cell cycle, plays a crucial role in regulation of cell proliferation.Aim. To evaluate the relationship of single-nucleotide polymorphisms (SNPs) of cell cycle genes with an increased frequency of СD in workers of a nuclear power plant affected by chronic occupational radiation exposure in the dose range of 100–500 mSv.Materials and methods. The object of the study was blood of 55 conditionally healthy workers of Siberian Chemical Plant (SCP) who were affected by chronic occupational radiation exposure (gamma radiation) in the dose range of 100–500 mSv. A standard cytogenetic analysis of blood lymphocytes was performed for all examined individuals. Genomic DNA was isolated from the blood of the workers using the QIAamp DNA Blood Mini Kit (QIAGEN, Germany). DNA was genotyped using 257 SNPs of cyclin genes and neighboring intergenic regions using DNA microarrays from the high-density CytoScan HD Array (Affymetrix, USA).Results. Taking into account the Bonferroni correction, only statistically significant associations of SNPs with the frequency of dicentric chromosomes were found; all other types of chromosomal aberrations did not show statistical significance. The rs803054 CCNI2 was associated with an increased frequency of dicentric chromosomes arising under the influence of chronic occupational radiation exposure.Conclusion. The discovered SNP (rs803054), whose recessive genotype is associated with an increased frequency of dicentric chromosomes in workers of SCP exposed to radiation at doses of 100–500 mSv over a long time, can be considered as a potential marker of individual radiosensitivity. To confirm the identified associations, further validation studies are needed on an expanded sample of people affected by chronic occupational radiation exposure.
BACKGROUND: Impaired apoptosis can have serious consequences: the accumulation of mutant cells, the development of teratogenic effects and malignant neoplasms. In this regard, the study of the mechanisms of changes in the activity of apoptosis due to methylation under the influence of long-term irradiation is urgent. AIM: The study of the degree of methylation of gene promoters involved in the induction of apoptosis in the personnel of the Siberian Chemical Plant, exposed to long-term technogenic irradiation of ionizing radiation in the course of their professional activities. MATERIALS AND METHODS: The study was performed on peripheral blood samples of employees of the Siberian Chemical Plant, with a total dose of external exposure from 100 to 300 mSv. Chromosomal aberrations were detected by standard karyotyping of cultured blood lymphocytes. The degree of gene promoters methylation was determined using MethylScreen technology. RESULTS: The degree of gene methylation BIRC2, CASP3, CASP9, CIDEB, CRADD, DAPK1, DFFA, FADD, GADD45A, LTBR, TNFRSF21, TNFRSF25 ranges from 0.31 to 41.75%. A strong negative correlation was found between the degree of methylation of GADD45A (r = 0.7364, р = 0.009) with an increased frequency of aberrant cells, moderate negative correlation GADD45A (r = 0.6347, р = 0.035) with an increased frequency of dicentric chromosomes, moderate negative correlation CASP9 (r = 0.6606, р = 0.026), and strong negative correlation CIDEB (r = 0.7982, р = 0.003) with an increased frequency of chromatid fragments. A moderate negative correlation of the methylation degree of CASP9 (r = 0.6636, р = 0.026), and CIDEB (r = 0.6636, р = 0.026) with the total dose of external exposure was shown. CONCLUSIONS: The decrease in the level of apoptosis at doses of 100300 mSv can be explained by the achievement of the demethylation threshold for the promoters of the proapoptotic genes GADD45A, CASP9, CIDEB. This once again testifies in favor of the threshold model of the dependence of the radiation effect on the radiation dose.
Purpose: Description of the collection, structure and development dynamics during the period from 2015 to 2019 of the biological material bank of the Seversk Biophysical Research Center, as well as research works carried out using biological material from its collection. Material and methods: The collection of bank of biological material includes the following types of biological material: venous blood, genomic DNA of white blood cells, cytogenetic suspensions of blood lymphocytes, surgical, biopsy and autopsy material. Biological material was obtained from people exposed to chronic radiation exposure: employees of the nuclear industry and the population permanently residing in the territory located in the area of the nuclear industry. Results: At present, the collection of the biological material bank contains more than 21,000 samples of biological material obtained from more than 8,000 donors. The collection of bank of biological material is represented by 4 main blocks: biological material of conditionally healthy employees of company of the nuclear industry (Siberian Chemical Combine); biological material of conditionally healthy people permanently residing in the territory located in the area of the nuclear industry enterprise (Seversk); biological material of patients (workers of the Siberian Chemical Combine and residents of Seversk) with malignant neoplasms and biological material of patients (workers of the Siberian Chemical Combine and residents of Seversk) with acute myocardial infarction. In the collection of bank of biological material, the proportion of samples of biological material of relatively healthy workers of the Siberian Chemical Combine is 33 %, residents of Seversk — 40.8 %, patients with malignant neoplasms — 22.2 %, patients with acute myocardial infarction — 4 %. Conclusion: Biological material bank Seversk Biophysical Research Center is unique collection of biological material samples of healthy people and patients with socially significant diseases. A feature of the biological material of the biological material bank is that it is obtained from people who have been exposed to chronic low-intensity radiation exposure and can be used to evaluate its radiogenic effects.
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