Search

Breast cancer is a widespread oncological disorder, which is considered one of the leading causes of mortality among women. DNA repair processes a well as its methylation involving genes of folate cycle play a crucial role in cancerogenesis. The aim of the study is to generalize the current data about association between polymorphic variants of folate cycle genes MTHFR С677Т (rs1801133), MTR A2756G (rs1805087), MTRR А66G (rs1801394) with risk of breast cancer development. The search of scientific papers has been conducted using PubMed and elibrary.ru sources. Original and randomized surveys published from 2008 till 2022 have been included in this review. The study has accumulated sufficient data on MTHFR С677Т polymorphic variant in breast cancer patients, having significant influence on disease development. However, the data about MTR A2756G and MTRR A66G variants is quite limited. According to the findigs of many scientific papers, there is no link between polymorphic variants of these genes and breast cancerogenesis manifestation. Such factors like ethniсity and sufficient consumption of folates with nutrition can have significant impact on results and conclusions of studies about role of folate cycle genes in breast cancer patients. Further investigation of MTHFR С677Т (rs1801133), MTR A2756G (rs1805087) and MTRR А66G (rs1801394) genetic polymorphic variants with consideration of gene-environment and gene-gene interactions could explain the presence of individual differences of breast cancer risk.

Plant polyphenols possess diverse medicinal and therapeutic properties. For instance, they can prevent such age-related diseases as stroke, heart attack, type II diabetes, and their various pathological complications. Mangiferin is a polyphenolic compound with a C-glycosylxanthone structure. This biologically active substance is known for its antioxidant, anti-inflammatory, antimicrobial, antidiabetic, and immunomodulatory properties. This research features mangiferin isolated fromHedysarum neglectumL. root culture and its effect on fat accumulation inCaenorhabditis elegansN2 Bristol. A set of experimentsin vivoproved that mangiferin was able to inhibit fat accumulation in the model organism. The optimal concentration was determined as 50 μm: it provided 44.5% fluorescence.

BACKGROUND: The micronucleus test of peripheral blood lymphocytes provides a qualitative assessment of the state of the genome. A study was carried out aimed at studying the influence of factors of the working environment of coal-fired power plants on the state of the DNA of working data of enterprises. MATERIALS AND METHODS: Using a micronucleus test with a cytochalasin block on human blood lymphocytes in vitro, 116 men were examined: 45 employees of the Novo-Kemerovo coal-fired power plant and 71 healthy residents of the Kemerovo region. RESULTS: An increase in the frequency of occurrence of cells with micronuclei, bridges and protrusions in the blood lymphocytes of workers of a coal-fired power plant in comparison with healthy residents of the same area was found. CONCLUSION: The data confirm the existing idea of the potential danger of combustion products for human health.

Introduction. Working conditions at coal-fired power plants cause an increased risk of the formation of chromosomal damage in workers. The contribution of the variability of the structure of the genes controlling the cell cycle and apoptosis to the occurrence of cytogenetic disorders induced by such mutagens has been little studied. Material and methods. The polymorphic variants of the genes: TP53 (rs1042522), CHEK2 (rs555607708), ATM (rs1801516), TGF-β1 (rs1800469), and the level of chromosomal aberrations (CA) in the lymphocytes of the blood were studied. Three hundred twenty-six workers of coal-fired power plants and 267 individuals who did not work in industrial enterprises were examined. All individuals were Caucasians, residents of Kemerovo (Western Siberia, Russia). Results. The level of CA in blood lymphocytes in thermal power plant workers was established to be statistically significantly higher than that of residents of the same locality who never works in industrial enterprises (3.05 ± 0.09% versus 1.67 ± 0.07%, p = 0, 000001). The prevalence of the polymorphic variants of the TP53 (rs1042522), CHEK2 (rs555607708), ATM (rs1801516), TGF-β1 (rs1800469) genes in the group of workers was the same to those in the comparison group and corresponded to the global data obtained in Caucasians. In the group of workers with the TT genotype of the TGF-β1 gene, the frequency of metaphases with chromosome damage was statistically significantly higher than in individuals with the CC genotype (4.07 ± 0.41% versus 2.85 ± 0.10%, p = 0.006). Discussion. For the first time a significant contribution of polymorphic variants of TGF-β1 genes to the formation of chromosomal damage in working coal-fired power plants was revealed. This may be associated with an increased level of expression of the multifunctional cytokine TGF-β1 in owners of the TT genotype and its ability to influence proliferation, apoptosis, telomerase activity, and other critical cellular processes. Conclusion. The results of the study I, ndicate that not only the complex of industrial genotoxicants, but also individual genetic characteristics of the organism can influence on the formation of cytogenetic disorders in workers at thermal power plants.

Recent findings indicate that the microbiome may have significant impact on the development of lung cancer by its effects on inflammation, dysbiosis or genome damage. The aim of this study was to compare the sputum microbiome of lung cancer (LC) patients with the chromosomal aberration (CA) and micronuclei (MN) frequency in peripheral blood lymphocytes. In the study, the taxonomic composition of the sputum microbiome of 66 men with untreated LC were compared with 62 control subjects with respect to CA and MN frequency and centromere fluorescence in situ hybridisation analysis. Results showed a significant increase in CA (4.11 ± 2.48% versus 2.08 ± 1.18%) and MN (1.53 ± 0.67% versus 0.87 ± 0.49%) frequencies, respectively, in LC patients as compared to control subjects. The higher frequency of centromeric positive MN of LC patients was mainly due to aneuploidy. A significant increase in Streptococcus, Bacillus, Gemella and Haemophilus in LC patients was detected, in comparison to the control subjects while 18 bacterial genera were significantly reduced, which indicates a decrease in the beta diversity in the microbiome of LC patients. Although, the CA frequency in LC patients is significantly associated with an increased presence of the genera Bacteroides, Lachnoanaerobaculum, Porphyromonas, Mycoplasma and Fusobacterium in their sputum, and a decrease for the genus Granulicatella after application of false discovery rate correction, significance was not any more present. The decrease of MN frequency of LC patients is significantly associated with an increase in Megasphaera genera and Selenomonas bovis. In conclusion, a significant difference in beta diversity of microbiome between LC and control subjects and association between the sputum microbiome composition and genome damage of LC patients was detected, thus supporting previous studies suggesting an etiological connection between the airway microbiome and LC.

Background. Active ribosomal genes and DNA repair genes play an important role in restoring genome integrity. Therefore we were studied relationship of active ribosomal genes dose and DNA repair genes polymorphisms with high level of chromosomal disorders in miners. Materials and methods. The DNA damage level was assessed using chromosomal aberrations (CA) at 288 coal miners and 676 men in the control group. The dose of active ribosomal gene (AcRG) has been analyzed using Ag-NORS staining regions of chromosomes and cytogenetic semi-quantitative evaluation method. Real-time PCR and allele-specific PCR techniques were used to analyze polymorphic variants of the XPG (rs17655), XPD (rs13181), XRCC2 (rs3218536), and XRCC3 (rs861539) genes. Results. A statistically significant ( p = 0.0001) increase of the СА level at miners was found in comparison with the control group. The association XPD 2251T > G locus with increasing CA level is revealed of in recessive inheritance model ( p adj = 0.0001). The association XPG 3310G > C locus with increasing СА level is revealed at the smoking workers ( p adj = 0.017). An average dose of AcRG was registered a statistically significant increase in the frequency of single fragments ( p = 0.016) at the miners. Conclusion . The obtained data on associations of chromosomal aberrations with different variants of DNA repair genes and the dose of active ribosomal genes are useful for the formation of high-risk groups.

The level of cytogenetic damage was analyzed in coal miners (N = 116) and the control sample (N = 169) using an assay for scoring of chromosomal aberrations (CAs) and the DNA comet assay in lymphocytes, as well as the micronucleus test in buccal epithelial cells (MN in BEC). The group of coal miners was characterized by a statistically significantly increase in the main index values of the used test system, compared to the control group. Specifically, the level of chromosomal aberrations in the miner and control groups was 4.69 ± 0.28 and 2.13 ± 0.10%; the proportion of DNA in the comet tail was 4.33 ± 0.38 and 2.16 ± 0.24%; and the micronucleus level was 1.44 ± 0.21 and 0.23 ± 0.12‰, respectively (Р < 0.05). Moreover, in the sample of coal miners, a considerable increase in the levels of additional test indices was observed. For CAs, these parameters included the frequency of single fragments, chromatid-type aberrations, paired fragments, dicentrics without fragments, chromosome exchanges, and chromosome-type aberrations; for the DNA comet assay, these were the comet tail moment and Olive tail moment; for the MN in BEC, the frequencies of binucleated cells, cells with notched nuclei, geminate nuclei, karyorhexis, and apoptotic bodies. Ranking of the results according to major cytogenetic abnormalities made it possible to establish that, in the group of miners, the proportion of individuals with the index values above the background was 68.97% for CAs, 52.13% for the DNA comet assay, and 36.08% for the MN in BEC. The proportion of individuals with cytogenetic damage higher than the background simultaneously in three test systems was 20% of the total sample of miners. To assess the mutagenic effects from occupational factors of coal mining enterprises, it seems reasonable to use a complex of test systems (CA test, DNA comet assay, and MN in BEC).

Polymorphic variants of genes of enzymes of xenobiotic biotransformation (CYP1A1 (rs4646903), CYP1A2 (rs762551), CYP2D6 (rs35742686), CYP2E1 (rs2031920), EPHX1 (rs1051740), GSTP1 (rs1138272, rs1695), GSTM1 (del), GSTT1 (del)), DNA reparation (XRCC1 (rs25489, rs25487, rs1799782), APEX1 (rs1130409), hOGG1 (rs1052133), PARP1 (rs1136410), XPD (rs13181), XPG (rs17655), XPC (rs2228001), ATM (rs1801516), NBS1 (rs1805794), XRCC2 (rs3218536), XRCC3 (rs861539), XRCC4 (rs2075685), Ligase IV (rs1805389)), antioxidant system (SOD2 (rs4880), GPx1 (rs1050450), CAT (rs1001179)), cell cycle control and apoptosis (TP53 (rs1042522)), cytokines (TGFβ (rs1800469), TNFα (rs1800629)), folate metabolism (MTHFR (rs1801133), MTR (rs1805087)), and chromosomal aberrations in blood lymphocytes of 288 miners of coal mines in Kuzbass, 365 workers of coal-fired thermal power plants, and 642 residents of Kemerovo oblast who did not work at industrial enterprises were analyzed. The frequency of chromosomal aberrations in the group of miners (4.06 ± 0.15%) and workers at thermal power plants (3.19 ± 0.09%) was significantly higher than in the group of individuals who did not work in production (1.53 ± 0.05%, p < 0.00001). The increased frequency of chromosome aberrations in miners is associated with genetic variants XPD rs13181 and XRCC4 rs2075685, and in power engineers with variants of the TGFβ gene rs1800469.

Introduction. Coal industry is one of the main economy sectors of many countries. However, it poses a danger to the environment and human health. Since the Kemerovo region is a region with a developed industry, the problem of maintaining genetic homeostasis is highly relevant. Miners are exposed to various harmful factors that can act as genotoxicants and cause various DNA damage.The aim of the study was to explore the associations of polymorphic variants of DNA repair genes with chromosomal instability in coal mining workers.Materials and methods. Polymorphic variants of genes of enzymes of reparation DNA (XPD (rs13181), XPG (rs17655), XRCC2 (rs3218536), XRCC3 (rs861536), XRCC4 (rs2075685), XRCC4 (rs1805377)) and chromosomal aberrations in blood lymphocytes of 307 miners of coal mines in Kuzbass, 338 residents of the Kemerovo region who did not work in industrial enterprises were analyzed.Results. The frequency of chromosomal aberrations in the group of miners (4.01±0.14) was significantly higher than in the group of individuals who did not work in production (1.67±0.06, pConclusions. Coal production has a negative impact on the genome of workers and can lead to the formation of cytogenetic disorders, which determines the need to develop measures for the comprehensive prevention of diseases caused by the accumulation of DNA damage. The results of the study will expand the existing understanding of the formation of the human genetic apparatus individual sensitivity to the effects of genotoxic factors, as well as formulate recommendations for coal mining workers in accordance with their genetic characteristics.Conflict of interests. The authors declare no conflict of interests.

The results of the study of chromosomal aberrations and micronuclei in blood lymphocytes, as well as micronuclei in buccal epithelium cells of 50 untreated men with lung cancer (LC) and 62 control donors, are presented. Using a variety of cytogenetic tests, a significant unidirectional increase in the base level of genetic instability in the cells of the patients was detected compared to the control. It was shown that, in LC patients, the elimination of damaged cells occurs predominantly by necrosis, whereas the frequencies of cells at the apoptosis stage do not differ in patients and control. The age of the patient, smoking status, type, and stage of LC do not have a significant impact on the performance of the baseline level of genetic damage. This fact suggests that the cytogenetic instability of the somatic cells of untreated LC patients is a constant sign that characterizes the genome response to the effect of the oxidative stress accompanying the neoplastic process.

This paper presents a review of research devoted to the study of genotoxic and carcinogenic effects of exposure to factors of the production environment of the coal mining and coal processing industries. The first part of the review analyzes mutagenic effects: chromosomal aberrations (CA), sister chromatid exchanges (SCE), micronuclei (MN), and DNA comets in coal mining workers (mines) and workers in coal processing (coal heating plants, coking plants) enterprises. The second part is devoted to the study of cancer incidence in workers employed in the coal industry. The third part deals with works that carried out a comprehensive analysis of the mutagenic and carcinogenic effects in miners and workers at coal-fired power plants and coking plants. In general, the analysis of the literature confirmed the high genotoxic and carcinogenic danger of the working conditions for workers employed in the coal mining and coal processing industry.

Working in coal mines, despite all achievements of modern science and technology, still remains among the most dangerous occupations to the health. The review of researches about the chromosomal damage in coal miners was performed. We searched information in the following databases - PubMed, http://www.sciencedirect.com and in the electronic library http://elibrary.ru with the use of the search strategy adopted in the Cochrane Collaboration. Inclusion criteria were: 1) randomized, controlled original researches; 2) researches performed in 1993-2016 where coal miners were the object of the study; 3) articles described chromosomal aberrations (CAs), micronuclei (MN), sister chromatid exchanges (SCE), DNA comets as biomarkers of the exposure. Exclusion criteria were other methods of the assessment of DNA damage; lack of data on the type of mines or coal mines/open-cast mines (uranium, tin, etc.); lack of access to the full text in Russian or English. As a result of the search 12 articles met selection criteria and showed a chromosomal damage in miners were selected. The results of researches performed in different countries (Russia, Turkey, Brazil, Colombia, Netherlands, Peru and India) demonstrate the increased frequency of chromosomal abnormalities in employees of coal mining industry. Damages are accumulated in cells of different types (buccal epithelium and lymphocytes) and can be detected by methods of the assessment of CAs, SCE, MN and DNA comet assay that indicating the complex basis of genotoxicants. The results of the analysis of the relationship between the cytogenetic markers, age and length of service are contradictory. The formation of occupational pulmonary diseases is accompanied by an additional induction of cytogenetic damage. In general, the analysis confirmed the high genotoxic risk of working conditions in underground as well as open-cast miners.

Objectives: The microbiome of sputum from former and active coal miners diagnosed with coal worker’s pneumoconiosis (CWP) as compared to healthy controls Methods: Next Generation Sequencing of bacterial 16S rRNA genes obtained from the sputum of CWP subjects.Results: Differences were detected between the sputum microbiomes from the healthy and CWP subjects. We noted a significant decrease in Bacteroidetes and an increase in the level of Proteobacteria.Conclusions: The microbiomes found in sputum from CWP subjects are enriched in bacterial species previously reported to induce pro-inflammatory responses. The profile of the microbiomes correlated mainly to the occupational activity and not to the age of the coal miners.

Respiratory tissues are highly susceptible to diseases due to the constant exposure to physical and chemical airborne pollutants. Chronic obstructive pulmonary disease (COPD) and lung cancer are among the most common causes of serious illness and death worldwide. The inflammatory environment associated with these respiratory diseases has long been accepted as the major player in the development of airway abnormalities. The presence and relevance of DNA damage and genomic instability makes the micronucleus assay a suitable candidate to quantitatively estimate these early pathogenetic events. A systematic review and meta-analysis were planned to determine underlying common mechanisms that can explain the relationships between COPD and lung cancer. A total of 17 studies from Jan 1999 to Dec 2019 comparing micronucleus frequency in patients affected by respiratory diseases vs healthy controls were analysed. Our results confirmed the presence of significant association between MN frequency and the diseases investigated, and suggested a circle of events linking inflammation induced oxidative stress to the risk of disease through genomic instability and hypoxia. Therefore, using non-invasive, robust and cost effective genomic instability assays such as the micronucleus assay, would allow us to capture unique phenotypic and biological changes that would allow the identification of subjects at high risk of developing lung diseases and improve early detection strategies.

Here we report a pilot-sized study to compare the taxonomic composition of sputum microbiome in 17 newly-diagnosed lung cancer (LC) patients and 17 controls. Another object was to compare the representation of individual bacterial genera and species in sputum with the frequency of chromosomal aberrations in the blood lymphocytes of LC patients and in controls. Both groups were male; average age 56.1 ± 11.5 in patients and 55.7 ± 4.1 in controls. Differences in the species composition of bacterial communities in LC patients and controls were significant (pseudo-F = 1.94; p = 0.005). Increased prevalence in LC patients was detected for the genera Haemophilus and Bergeyella; whereas a decrease was observed for the genera Atopobium, Stomatobaculum, Treponema and Porphyromonas. Donors with high frequencies of chromosomal aberrations had a significant reduction in the microbiome of representatives of the genus Atopobium in the microbiome and a simultaneous increase in representatives of the species Alloprevotella compared to donors with a low level of chromosomal aberrations in lymphocytes. Thus, a comparison of the bacterial composition in the sputum of donors with cytogenetic damages in theirs lymphocytes, warrants further investigations on the potential role of microorganisms in the process of mutagenesis in somatic cells of the host body.

Mitomycin C (MMC) is an alkylating chemotherapy drug that causes DNA crosslinking resulting in transcription arrest and apoptosis. DNA crosslinking is a critical damage to DNA that can be caused not only by MMC and other antitumor drugs, but also by various environmental and anthropogenic endo- and exogenous agents. Mammalian cells exposed to alkylating mutagens are characterized by severe genotoxic stress. Somatic mutations and genotoxic stress may lead to endothelial dysfunction, which is the initial stage of atherosclerosis, a leading cause of morbidity and mortality worldwide. Here we studied DNA damage, protein secretion and gene expression of IL6 and IL8 in primary human coronary artery endothelial cells (HCAEC) and human internal thoracic artery endothelial cells (HITAEC) in vitro exposed to 500 ng/mL MMC. We observed an increase in levels of cytogenetic damage (micronuclei, nucleoplasmic bridges and nuclear buds) in MMC-treated cells compared to control cells. After 6 h incubation with MMC, both HCAEC and HITAEC displayed a decrease in IL8 concentration and the mRNA level of IL6 and IL8 compared to control cells. Removal of MMC from cultures after 6 h followed by 24 h incubation of cells in complete growth media led to a sharp increase in secretion and gene expression of the studied cytokines in both HCAEC and HITAEC. Moreover, HCAEC were more susceptible to mutagenic exposure compared to HITAEC. These findings suggest that the MMC-induced genotoxic stress in endothelial cells derived from different arteries is associated with differential secretion and gene expression of proinflammatory cytokines IL6 and IL8.

Anthracosilicosis (AS), a prevalent form of pneumoconiosis among coal miners, results from the accumulation of carbon and silica in the lungs from inhaled coal dust. This study investigated genotoxic effects and certain cytokine genes polymorphic variants in Russian coal miners with АS. Peripheral leukocytes were sampled from 129 patients with AS confirmed by X-ray and tissue biopsy and from 164 asymptomatic coal miners. Four single-nucleotide polymorphisms were genotyped in the extracted DNA samples: IL1β T-511C (rs16944), IL6 C-174G (rs1800795), IL12b A1188C (rs3212227) and VEGFA C634G (rs2010963). Genotoxic effects were assessed by the analysis of chromosome aberrations in cultured peripheral lymphocytes. The mean frequency of chromatid-type aberrations and chromosome-type aberrations, namely, chromatid-type breaks and dicentric chromosomes, was found to be higher in AS patients [3.70 (95% confidence interval {CI}, 3.29-4.10) and 0.28 (95% CI, 0.17-0.38)] compared to the control group [2.41 (95% CI, 2.00-2.82) and 0.09 (95% CI, 0.03-0.15)], respectively. IL1β gene T/T genotype (rs16944) was associated with AS [17.83% in AS patients against 4.35% in healthy donors, odds ratio = 4.77 (1.88-12.15), P < 0.01]. A significant increase in the level of certain chromosome interchanges among AS donors is of interest because such effects are typical for radiation damage and caused by acute oxidative stress. IL1β T allele probably may be considered as an AS susceptibility factor among coal miners.

The 23 polymorphic variants in genes encoding the enzymes of xenobiotics biotransformation (CYP1A1 (rs4646903), CYP1A2 (rs762551), GSTP1 (rs1138272, rs1695), GSTM1 (del), and GSTT1 (del)), DNA repair (XRCC1 (rs25489, rs25487), APEX1 (rs1130409), hOGG1 (rs1052133), ADPRT (rs1136410), XPD (rs13181), XPG (rs17655), XPC (rs2228001), ATM (rs1801516), NBS (rs1805794), XRCC2 (rs3218536), and XRCC3 (rs861539)), antioxidant system (MnSOD (rs4880) and GPx1 (rs1050450)), cell cycle control and apoptosis (TP53 (rs1042522)), DNA methylation (MTHFR (rs1801133) and MTR (rs1805087)), and chromosomal aberrations in lymphocytes in the workers at thermal power plants were analyzed. We found that allelic variants in the CYP1A1 (rs4646903), hOGG1 (rs1052133), XRCC1 (rs25487), and APEX1 (rs1130409) genes were associated with an increased level of chromosomal aberrations in workers. Informative models of gene-gene interactions including CYP1A1 (rs4646903, T>C), CYP1A2 (rs762551, C>A), GSTT1 (del); XRCC1 (rs25487, G>A), MTHFR (rs1801133, C>T), GSTT1 (del); XRCC1 (rs25487, G>A), APEX1 (rs1130409, T>G), TP53 (rs1042522, G>C) determining the formation of the increased frequency of chromosomal aberrations in the workers at coal thermal power plants were discovered.

Background. Maintaining radon safety is one of the most critical challenges in modern ecology and genetic toxicology. Radon (222Rn) and its decay daughter products (218Po, 214Po, 214Pb and 214Bi) can interact with biological tissues and induce DNA damage. Because transcribed copies rDNA are necessary for DNA damage repair, we examined whether genomic dosages of active ribosomal genes modulate the genotoxic effects of exposure to high doses of radon. Materials and methods. Chromosome aberration assay in peripheral blood lymphocytes was performed in pupils of the boarding school of Tashtagol (Kemerovo region, Russia) with long-term resident exposure to radon (n = 345) and in childrenof the Kemerovo Region living in radiation-safe conditions (n = 233). The dose of active (transcription-capable) ribosomal gene (AcRG) in the studied groups has been analyzed using Ag-NORS staining regions of chromosomes and cytogenetic semi-quantitative evaluation method. Results. A statistically significant increase in the level of chromosome aberrations in exposure group has been revealed compared with the children of the Kemerovo Region living in radiation-safe conditions (p = 0.00001). It was found that the level of chromosomal abnormalities in Tashtagols children was higher in medium-dose carriers of AcRG compared to owners of a low dose (4.27 0.22% vs. 3.24 0.29%, p = 0.003). Perhaps the low level of chromosomal aberrations in children with low-dose AcRG is associated with an increase in cell death from damaged DNA under genotoxic exposure to radon. Conclusion. The obtained results testify to the significant contribution of the individual characteristics of ribosomal genes in the formation of genotoxic effects of exposure to high doses of radon.

We analyzed the polymorphic loci in the genes of the antioxidant system enzymes, such as GSTP1 (313A>G and 341C>T), MnSOD (47С>Т), GPx1 (599C>T), and CAT (–262C>>T), among 497 residents of Kemerovo oblast (Western Siberia, Russia). The analysis of the single-locus effects demonstrated a significant protective effect of the major C allele in the GPx1 (599C>T) locus. The MDR analysis of the gene-gene interactions showed that the GPx1 and the CAT genes work in close cooperation and mutually reinforce the risk of development of squamous cell lung cancer among the inhabitants of the industrial region.

New molecular cytogenetic biomarkers may significantly contribute to biodosimetry, whose application is still globally diverse and not fully standardized. In 2011, a new term, chromothripsis, was introduced raising great interest among researchers and soon motivating further investigations of the phenomenon. Chromothripsis is described as a single event in which one or more chromosomes go through severe DNA damage very much resembling rogue cells (RC) described more than 50 years ago. In this review, we for the first time compare these two multi-aberrant cells types, RC versus chromothriptic cells, giving insight into the similarities of the mechanisms involved in their etiology. In order to make a better comparison, data on RC in 3366 subjects from studies on cancer patients, Chernobyl liquidators, child victims of the Chernobyl nuclear plant accident, residentially and occupationally exposed population have been summarized for the first time. Results of experimental and epidemiological analysis show that chromothriptic cells and RC may be caused by exposure to high LET ionizing radiation. Experience and knowledge collected on RC may be used in future for further investigations of chromothripsis, introducing a new class of cells which include both chromothriptic and RC, and better insight into the frequency of chromothriptic cell per subject, which is currently absent. Both cell types are relevant in investigations of cancer etiology, biomonitoring of accidentally exposed population to ionizing radiation and biomonitoring of astronauts due to their exposure to high LET ionizing radiation during interplanetary voyages.

Air pollutants and ionizing radiation are well-known carcinogens involved in the pathogenesis of lung cancer, and residents of coal-mining regions are exposed routinely to these agents. Polymorphisms in DNA repair genes may be associated with an increased risk of malignant transformation. We investigated associations between the risk of lung cancer in residents of the coal-mining region and polymorphisms in the genes APEX1 (rs1130409), hOGG1 (rs1052133), XRCC1 (rs25489, rs25487), XRCC2 (rs3218536), XRCC3 (rs861539), ADPRT/PARP1 (rs1136410), XPD/ERCC2 (rs13181), XPG/ERCC5 (rs17655), XPC (rs2228001), ATM (rs1801516), and NBS1 (rs1805794). Three hundred and forty residents of the Kemerovo Region (a coal-mining region of western Siberia) were lung cancer patients exposed to air pollutants and ionizing radiation (case) and 335 were healthy donors (control). Genotyping was performed by real-time PCR and allele-specific PCR. We discovered that polymorphisms in the XPD gene in men [log-additive model: odds ratio (OR) = 1.64, 95% confidence interval (CI): 1.17-2.31], the ATM gene in women and nonsmokers (codominant model: OR = 0.11, 95% CI: 0.02-0.49 and OR = 0.25, 95% CI: 0.08-0.72, respectively), the APEX1 gene for smokers (recessive model: OR = 2.55, 95% CI: 1.34-4.85), and the NBS1 gene for those who work in the coal industry (overdominant model: OR = 0.40, 95% CI: 0.21-0.75) are associated with an increased risk of lung cancer. Using the multifactor dimensionality reduction method, we found a model of gene-gene interactions associated with the risk of lung cancer: NBS1 (rs1805794)-XRCC1 (rs25487)-hOGG1 (rs1052133)-XPG (rs17655). These results indicate an association between combinations of polymorphisms in the studied genes and the risk of lung cancer in residents of a coal-mining region.

The level and range of chromosomal aberrations in residents of Kemerovo, a large industrial center of Western Siberia, was studied in two periods of time: from 1986 to 2000 and from 2001 to 2012. Cytogenetic studies were performed on 668 persons (333 persons in the first period and 335 persons in the second period). The frequency of aberrations among residents in Kemerovo was lower in 2001–2012 than in 1986–2000, which is consistent with the reduced emission of pollutants into the air in Kemerovo. The new background level of chromosomal aberrations in Kemerovo’s residents, who do not come into contact with industrial genotoxicants, was established at 1.48 ± 0.08% and can be used in further genetic and ecological studies.

Coal miners are exposed to a wide range of genotoxic agents that can induce genome damage. In addition, miners are characterised by a high risk of the initiation of different occupational inflammatory as well as non-inflammatory diseases. The aim of this investigation is to analyse the modifying influence of occupational pulmonary inflammatory diseases on the level of chromosome aberrations (CAs) in miners working in underground coal mines in Kemerovo Region (Russian Federation). The study group included 90 coal miners with the following pulmonary diseases: chronic dust-induced bronchitis (CDB) and coal-workers' pneumoconiosis (CWP) (mean age = 53.52±2.95 years; mean work experience in coal-mining conditions = 27.70±3.61 years). As a population control (control 1), we have used venous blood extracted from 124 healthy unexposed men. The mean age in this group was 50.92±4.56 years. Control 2 was the venous blood extracted from 42 healthy coal miners (mean age = 51.56±6.38 years; mean work experience in coal-mining conditions = 25.43±8.14 years). We have discovered that coal miners are characterised by an increased general level of CAs as well as an increased frequency of several types of CAs. The significant increase in the frequency of aberration per 100 cells and aberration of chromosome type was discovered in the group of pulmonary disease patients (study group). No correlations of the level of chromosome damage with age, smoking status and work experience in coal-mining conditions were discovered.

DNA samples from 318 children and adolescents (174 males, 144 females), exposed to radon at home and 65 children (23 males, 42 females) in the control group have been studied. Using the micronucleus test on buccal epithelial cells we identified a significant increase in the number of cells with cytogenetic and proliferative abnormalities in the exposed group. Associations between NBS1 (rs1805794), ATM (rs1801516), and ADPRT (rs1136410) genes polymorphisms and karyological abnormalities in buccal epithelial cells were investigated. For the exposed group, an association of NBS1 Glu185Gln polymorphism with an increased frequency of “broken egg”-type protrusions and apoptotic bodies was established. The NBS1 185Glu/Gln and the ATM1 1853Asp/Asp genotypes were associated with elevated levels of cytogenetic damage, while the NBS1 185Glu/Glu and ATM 1853Asp/Asn genotypes demonstrated a protective role. No significant associations were found in the control group.

In underground coal mining, numerous harmful substances and ionising radiation pose a major threat to the occupational safety and health of workers. Because cell DNA repair machinery eliminates genotoxic stress conferred by these agents, we examined whether single nucleotide polymorphisms in hOGG1 (rs1052133), XRCC1 (rs25487), ADPRT (rs1136410), XRCC4 (rs6869366) and LIG4 (rs1805388) genes modulate the genotoxic damage assessed by the cytokinesis-block micronucleus assay in lymphocytes from 143 underground coal miners and 127 healthy non-exposed males. We also analyzed models of gene-gene interactions associated with increased cytogenetic damage in coal miners and determined 'protective' and 'risk' combinations of alleles. We showed that miners with the G/G genotype of the hOGG1 (rs1052133) gene had a significantly increased frequency of binucleated lymphocytes with micronuclei (13.17‰, 95% CI = 10.78-15.56) compared to the C/C genotype carriers (10.35‰, 95% CI = 9.59-11.18). In addition, in the exposed group this indicator was significantly increased in carriers of the T/T genotype of the LIG4 (rs1805388) gene compared to miners harbouring the C/T genotype (13.00‰, 95% CI = 10.96-15.04 and 9.69‰, 95% CI = 8.32-11.06, respectively). Using the multifactor dimensionality reduction method, we found the three-locus model of gene-gene interactions hOGG1 (rs1052133) × ADPRT (rs1136410) × XRCC4 (rs6869366) associated with high genotoxic risk in coal miners. These results indicate that the studied polymorphisms and their combinations are associated with cytogenetic status in miners and may be used as molecular predictors of occupational risks in underground coal mines.

To study the potential links between genetic polymorphisms in the GSTT1, GSTM1, GSTP1 genes and the frequency of chromosomal aberrations (CAs) in lung cancer patients and healthy residents in Russian Federation. 200 cells in well-spread metaphase with 46 chromosomes were examined for 353 newly diagnosed lung cancer patients (males) who received medical treatment in the Kemerovo Regional Oncology Center (Kemerovo, Russian Federation), and 300 healthy males from Kemerovo, Russian Federation. The polymorphisms of the GSTM1 del and GSTT1 del genes were analysed by multiplex PCR. Genotyping of the polymorphic variants in the GSTP1 (A313G, T341C) gene was performed using Real-time PCR with competing TaqMan probes complementary to the polymorphic DNA sites. The data analysis was performed using software STATISTICA 8.0 (StatSoft Inc., USA). We discovered that a GSTM1 del polymorphism increases the frequency of chromosomal damage in smoking patients with lung cancer, a general group of lung cancer patients, donors with non-small cell lung cancer and patients in the latest stages of the malignant process. The synergetic effects of occupational exposure and the malignant process can induce some modifications in the cytogenetic status in lung cancer patients harbouring the GSTM1 del polymorphism. CAs in peripheral blood lymphocytes can be used as biomarkers of the early biological effects of exposure to genotoxic carcinogens and may predict future cancer incidence in several epidemiologic studies. Genetic changes in genes encoding phase II detoxification enzymes are linked to decreases in the metabolic detoxification of environmentally derived genotoxic carcinogens.

Background. The level and range of chromosomal aberrations in inhabitants of Kemerovo, a large industrial center of Western Siberia, were studied in two time periods: from 1986 to 2000 and from 2001 to 2012. Materials and methods. Total of 668 inhabitants were examined for chromosomal aberrations in their blood lymphocytes: 333 in the first time period and 335 in the second one. Official data on emission of air pollutants in Kemerovo, obtained by the Center for Hygiene and Epidemiology in the Kemerovo region in the period from 1986 to 2012, were also analyzed.Results. We found that frequency of aberrations among residents in Kemerovo was lower in 2000s as compared to the previous time period studied, which is consistent with reduced emission of pollutants into the air in Kemerovo. The new value of the background level of chromosomal aberrations in Kemerovo residents not contacting industrial genotoxicants was established at 1.48 ± 0.08% and can be used in further genetic and ecological studies. Conclusion. Obtained results confirm coherence of environmental pollution and mutagenesis in populations of industrial cities.

The effects of LIG4 gene polymorphisms rs1805388 (Thr9lle) and rs1805389 (Ala3Val) on the level of chromosomal aberrations in the lymphocytes of peripheral blood was estimated for children that live and study in conditions of normal and supernormal radon exposure in several locations in Kemerovskaya oblast. A statistically significant difference of the cytogenetic values among genotypic groups with the use of marker rs1805388 was not shown. At the same time, in the group of Val carriers (marker rs1805389) from the second cohort of our analysis revealed a significant increase of the amount of paired fragments in comparison to homozygotes Ala/Ala.

Were investigated samples from 318 children and adolescents (174 males, 144 females), who were exposed to radon at home, and 65 people (23 males, 42 females) in the control group. Using micronucleus test on buccal epithelial cells we identified a significant increase in the number of cells with cytogenetic and proliferative abnormalities in the exposed group. Were investigated the association NBS1 (rs1805794), ATM (rs1801516), ADPRT (rs1136410) genes polymorphism with karyological abnormalities in buccal epithelial cells. For the exposed group, an association of NBS1 Glu185Gln polymorphism with increasing frequency of identification of “broken egg”-type protrusions and apoptotic bodies was established. NBS1 185Glu/Gln ATM1853Asp/Asp genotypes were associated with an elevated levels of cytogenetic damage, while the NBS1 185Glu/Glu ATM 1853Asp/Asn allelic variant plays a protective role. In the control group, no significant associations were found.

Effects of the LIG4 gene polymorphisms rs1805388 (Thr9Ile) and rs1805389 (Ala3Val) on the level of chromosomal aberrations in peripheral blood lymphocytes have been estimated in children, that live and study in conditions of normal and excessive exposure to radon in several localitions of the Kemerovo region. There was no statistically significant difference between genotypic groups on the marker rs1805388 with regard to frequencies of cytogenetic indexes. At the same time, in the group of Val carriers (marker rs1805389) from second cohort our analysis revealed significant increase in the amount of paired fragments in comparison with homozygotes Ala/Ala.

This work presents the results of research into the links between DNA-repair gene polymorphisms and chromosomal aberrations in lung-cancer patients. Significant positive links have been found between lung cancer and the hOGG1 G/G and XPD G/G genotypes. A significant negative association has been found between the hOGG1 C/C genotypes and lung cancer. It has been shown that metaphases with chromosomal aberrations were significantly more frequent in lung-cancer patients than in the control group. Levels of chromosomal aberrations in the carriers of all APE1 and XPD genotypes, XRCC1 G/G genotype, ADPRT T/T genotype, and hOGG1 C/C genotypes reliably differed between the study and control groups. Statistically significant differences have been found between the lung-cancer patients carrying the XPD T/T genotype and those with G/G genotype of this gene.

Coal miners are exposed to coal dust, containing mineral particles, inorganic compounds and polycyclic aromatic hydrocarbons, and to ionizing radiation. These factors can induce oxidative stress and promote inflammation that leads to DNA damage. The aim of this investigation is to analyse the degree of DNA damage in miners working in underground coal mines in Kemerovo Region (Russian Federation) using the cytokinesis-block micronucleus assay (CBMN) in peripheral blood lymphocytes. The exposed group included 143 coal miners (mean age = 50.11±7.36 years; mean length of service in coal mining conditions = 23.26±9.66 years). As a control group, we have used venous blood extracted from 127 healthy non-exposed men. The mean age in this group was 47.67±8.45 years. We have discovered that coal miners are characterized by a significant increase in the frequency of binucleated lymphocytes with micronuclei (MN), nucleoplasmic bridges (NPBs) and protrusions (NBUDs) compared to non-exposed donors. In addition, we report, for the first time, a reduction of cell proliferation in a cohort of coal miners. These data are evidence of the genotoxic and cytostatic effects of occupational harmful factors of the coal mining industry. No correlation between the level of chromosome damage and age, smoking status or length of service in coal mining conditions were discovered. We suggest that the CBMN assay would be useful in biomonitoring studies to monitor hygiene and prevention strategies in occupational settings in coal mining countries.

Lung cancer is one of the most common forms of cancer. The aim of this study was to validate chromosome aberrations in peripheral blood lymphocytes of lung cancer patients living in a region with high air pollution and increased background radon levels as a biomarker of cancer risk. A total of 417 lung cancer patients and 468 control participants were analysed using a chromosome aberration assay in peripheral blood lymphocytes. The results showed that chromatid-type aberrations (2.26±1.58 vs. 1.60±1.58) and chromosome-type aberrations (CSAs) (0.96±1.36 vs. 0.42±0.70) in lung cancer patients were increased significantly in comparison with the controls. The most significant two-fold increase was detected for CSAs (nonsmoking patients: 0.84±1.54 vs. 0.41±0.73%, smoking patients: 0.99±1.31 vs. 0.44±0.67%). The frequency of dicentric and ring chromosomes, double minutes and rogue cells was significantly higher (P=0.002, 0.00002, 0.01, 0.0007) in the lung cancer patients. As both analysed groups lived in the same environment, our results show that increased radon levels were not the only source for the detected genome damage. Using binomial logistic regression, the estimated odds ratios and 95% confidence intervals adjusted for the main confounders (smoking, occupational exposure, age) were 1.31 (1.20-1.40) for chromatid-type aberrations, 1.28 (1.17-1.33), and 1.68 (1.49-1.88) for CSAs. It may be suggested that lung cancer patients show a significant increase in genome damage that may be caused by an interplay between exposure and individual low capacity of DNA repair, leading to genome instability.

As children are more susceptible to ionizing radiation than adults, each nuclear accident demands special attention and care of this vulnerable population. The Chernobyl nuclear disaster occurred in a region populated with a large number of children, but despite all efforts and expertise of nuclear specialists, it was not possible to avoid casualties. As vast regions of Ukraine, Belarus and Russia were exposed to doses of ionizing radiation, which are known to be related with different diseases, shortly after the accident medical surveillance was launched, which also included analysis of genome damage. Child population affected by internal and external radiation consisted of subjects exposed prenatally, postnatally (both evacuated and non-evacuated), born by irradiated fathers who worked as liquidators, and parents exposed environmentally. In all groups of children during the last 30 years who were exposed to doses which were significantly higher than that recommended for general population of 1 mSv per year, increased genome damage was detected. Increased genome damage includes statistically higher frequency of dicentric and ring chromosomes, chromated and chromosome breaks, acentric fragments, translocations, and micronuclei. The presence of rogue cells confirmed internal contamination. Genome instability and radiosensitivity in children was detected both in evacuated and continuously exposed children. Today the population exposed to ionizing radiation in 1986 is in reproductive period of life and follow-up of this population and their offspring is of great importance. This review aims to give insight in results of studies, which reported genome damage in children in journals without language restrictions.

Analysis of the association between several DNA repair gene polymorphisms and the level of chromosomal aberrations (CAs) in lymphocytes of two groups of adolescents was carried out: in a group of 256 donors exposed to indoor radon and a control group of 94 donors. In a group of children with living conditions exposing them to high doses of radon (>200 Bq/m3), the level of CAs was significantly higher among carriers of genotypes hOGG1 Cys/Cys, hOGG1 Ser/Cys, ADPRT Ala/Ala, and ADPRT Val/Ala. No significant association between the level of CA and XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln, and APE1 Asp148Glu polymorphisms was found.

Analysis of association between several DNA repair gene polymorphisms and the level of chromosomal aberrations (CAs) in lymphocytes was performed in two groups of teenagers: a group of 256 donors exposed to indoor radon and a control group of 94 donors. In the group of children with living conditions exposing them to high doses of radon ( 200 Bq/m3 ), the level of CAs shows a significant increase in the carrier of genotypes: hOGG1 Cys/Cys, hOGG1 Ser/Cys, ADPRT Ala/Ala and ADPRT Val/Ala. Furthermore there were no significant associations between level of CA and Arg194Trp, Arg280His, Arg399Gln polymorphisms of the XRCC1 and Asp148Glu polymorphism of the APE1 found.

The correlation between the level of chromosomal aberrations and CYP1A genotypes in adolescents of the Tashtagol boarding school (Kemerovo region) exposed to a combined effect of high doses of radon and heavy metals has been studied. It was found that the level of chromosomal aberrations shows a statistically significantly increase in carriers of at least one CYP1A1*2A (A2455G) allele. The frequency of ring chromosomes shows a statistically significant increase in carriers of the CYP1A1 *1A*1A (T3801C) genotype. The frequency of multiple chromosomal aberrations was higher in carriers of the CYP1A2*1A*1A genotype. A conclusion on the important role of polymorphic CYP1A loci in genotoxic effects of radon and heavy metals is made.

The correlation between genotype CYP1A and level of chromosomal aberrations in adolescents which are living and learning in a boarding school of Tashtagol of Kemerovskaya oblast' in the conditions of complex genotoxic influence of raised concentration of radon and heavy metals has been studied. The levels of chromosomal aberrations were increased in carriers of at least one CYP1A1 *2A allele, as compared with CYP1A1*1A*A gomozygotes. Frequency of ring chromosomes it is significant it is raised at donors of genotype CYP1A1 *1A*1A (T3801C). Frequency of occurrence of lural chromosomal aberrations it is significant it is raised at donors with genotype CYP1A2 *1A*1A. The conclusion about the important role of CYP1A in formation genotoxic effects of complex influence of adon and heavy metals is made.

We present the results of cytogenetic monitoring of the districts in Kemerovo region, which differ in standardized indices of cancer incidence. It has been shown that residents of the districts with high incidence of malignancies had higher average frequency of metaphases with chromosomal aberrations than the control group (4.06 ± 0.12% and 2.76 ± 0.13%, respectively). This difference is caused primarily by single or paired fragments. The increase in the frequency of aberrant metaphase incidence in the districts with elevated cancer frequency was observed both in the male and female groups as well as both in adults and children.

Chromosomal aberration rate has been estimated in peripheral blood lymphocytes of subjects occupationally exposed to a set of hazardous factors (employees of the Kemerovo Heat Power Plant). The frequency of metaphases with aberrations in the workers (3.23 ± 0.26%, N = 104) is significantly higher than in control subjects (2.11 ± 0.28%, N = 70). The cytogenetic aberrations did not depend on the sex, age, duration of employment, or smoking.

GSTM1 and GSTT1 gene polymorphisms were studied in Shorians, Teleuts, and Caucasians of the Kemerovo region. It has been shown that distribution of homozygous deletions in the examined groups is significantly heterogeneous. The frequency of deletion genotypes and combinations of deletion in these genes was lower in Shorians and, Teleuts than in Caucasians.

In this study, the frequency and spectrum of chromosomal aberrations were analysed in samples of peripheral blood from 372 (mean age = 12.24 ± 2.60 years old) long-term resident children in a boarding school (Tashtagol city, Kemerovo Region, Russian Federation) under conditions of high exposure to radon and its decay products. As a control group, we used blood samples from people living in Zarubino village (Kemerovo Region, Russian Federation). We discovered that the average frequencies of single and double fragments, chromosomal exchanges, total number of aberrations, chromatid type, chromosome type and all types of aberrations were significantly increased in the exposed group. This is evidence of considerable genotoxicity to children living under conditions of high exposure to radon compared to children living under ecological conditions without increased radon radiation.