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The basis for the prevention of cancer is the correction of initial epigenetic disorders in the cell, i.e. implementation of pathological genome reversion. Convincing evidence has accumulated to support the potential antitumor activity of compounds derived from cruciferous vegetables of the genus Brassicaceae. Indole-3-carbinol and 3,3'-diindolylmethane (DIM) have been investigated for their use as chemopreventive agents. DIM is formed in the acidic environment of the stomach as a result of dimerization of indole-3-carbinol monomers. Currently, it is impossible to identify a specific vector of influence of DIM at the molecular level. In this review, we summarize the pleiotropic effects of DIM aimed at correcting reversible epigenetic changes in tumor cells. Emphasis will be placed on the major cellular and molecular events that are effectively modulated by DIM. The main profile of DIM competencies concerns the management of intracellular signal transmission and correction of initial molecular genetic changes at the level of key participants in signaling pathways (NF-κB/Wnt/Akt/mTOR) leading to the development of cancer. The ability of DIM to differentially modulate tumor cell apoptosis has been observed in preclinical studies. It has been suggested that using DIM it is possible to increase the effectiveness of chemotherapeutic compounds with different molecular targets, thereby increasing chemosensitization. DIM has entered phase III clinical trials, with preliminary results confirming its promise both as a stand-alone drug and in combination with other components of anticancer therapy. Establishing the range of epigenetic control of DIM molecular and genetic changes in various cancers will allow optimization of therapeutic epigenetics approaches.

The intestinal microbiota, having enormous metabolic potential, makes a significant contribution to the physiological and pathological processes of humans and animals and is currently considered as an important factor in the pathogenesis of cancer. The aim of this study is to determine changes in the quantitative and qualitative composition of the intestinal microbiota in Wistar rats during chemical induction of breast cancer (BC). Material and methods. The work was performed on female Wistar rats (n = 40) aged 3 months, weighing 200–210 g, using cultural methods for studying fecal microbiota in intact rats (1 group) on the 1st, 14th, 35th days and in rats with induction of breast cancer and and in rats, whereby N-methyl-N-nitrosourea was administered to induce breast cancer (2 group) on the 1st (before injection of N-methyl-N-nitrosourea), 14th, 35th days after injection of N-methyl-N-nitrosourea. Results and discussion. In all experimental animals, representatives characteristic of the intestinal normobiota of warm-blooded animals predominated, namely: Bifidobacterium spp., Lactobacillus spp., Escherichia coli with pronounced enzymatic properties, Enterococcus spp., Clostridium spp. In addition, Staphylococcus spp., yeast-like fungi of the genus Candida and mold. Escherichia coli with reduced enzymatic activity was also detected. It was established that the isolated bacteria belonged to 3 types, 4 classes, 5 orders, 6 families, 6 genera of the bacterial domain. Also, 2 genera of fungi belonging to the order Saccharomycetales were isolated. The most significant changes in the composition of the intestinal microbiota were noted in rats with chemically induced breast cancer on the 35th day tumor induction: the appearance of pathogenic microflora in the intestine was revealed.

It is known that chronic social stress leads to immunity disorders in humans and experimental animals. It has been shown that the effect of stress is also manifested in changes in the level of expression of genes involved in the functioning of various physiological systems in the brain of mice, in particular, in the hypothalamus. It was noted that in stressed animals, genes involved in the processes of carcinogenesis and apoptosis change their expression, and in animals without signs of developing a malignant process, but under conditions conducive to tumor growth. In this regard, we used the RNA-seq method to study the expression of cytokine response genes in the hypothalamus of male mice under the influence of chronic social stress caused by repeated experience of defeats in intermale confrontations, compared with control individuals. Multidirectional changes in the expression of cytokine genes, their receptors and genes performing a regulatory function were detected (IL17d, IL18, IL33, Csf1r, Csf2ra, IL11ra1, IL13ra1, IL2ra, IL3ra, IL5ra, Lifr, Cish, IL4i1, Irf1, Irf5, Irf9, Jak2, Socs3, Stat3, Tgfb1, Tlr3). Thus, it has been shown that changes in the cytokine response in the brain under the influence of stress occur at the level of changes in gene expression. In this case, we should not talk about the activation of the system or a decrease in its activity, but about the disruption of its functioning. Next, we analyzed the correlations between the level of expression of genes of the cytokine system and the main genes of carcinogenesis and apoptosis that we studied earlier (Akt1, Bag6, Foxp4, Mapk3, Mapk8, Nol3, Pdcd10, Xiap). The Akt1, Jak2, Stat3 genes were identified, for which the maximum number of correlations was found, moreover, negative correlations were most characteristic of Jak2, and positive correlations were most characteristic of Stat3 and Akt1. In addition, protein-protein interactions between genes of carcinogenesis and apoptosis and genes of the cytokine system were analyzed using the String database in mice under chronic social stress. It was confirmed the key role of these genes in the development of dysfunction of cytokines in the brain.

Background. In oncology, of particular interest is the study of the T-cell receptor excision circles (TREC) and the κ-deletion B-cell receptor excision circles (KREC), which are extrachromosomal DNA structures. In many malignancies, the effectiveness of immune checkpoint inhibitors depends on the mutational load of the tumor, which correlates with the formation of specific antitumor immunity. Quantitative indicators of recombination excision circles reflect the occurrence of a different repertoire of T-cell receptors, an integral component in the formation of specific immunity. Understanding the change in quantitative values of TREC and KREC in cancer patients can improve the selection of patients for immunotherapy. Aim. To determine quantitative indicators of TREC and KREC for immunological evaluation of patients with malignancies. Materials and methods. The study included 55 healthy individuals and 180 patients with malignancies. Among healthy individuals, 49.1% (27/55) were males and 50.9% (28/55) females. Among patients with malignancies, 20.5% (37/180) were males and 79.5% (143/180) females. The median age in healthy individuals was 36 years [Q1–Q3: 26–58]. The median age in the group of patients with malignancies was 57 years [Q1–Q3: 47.5–67]. Results. In the general population of healthy individuals, the median TREC level was 60.1 [Q1-Q3: 31.3-188.9] and the median KREC level was 256 [Q1-Q3: 149.8-353]. In the general population of patients with malignancies, the median TREC rate was 4.6 [Q1-Q3: 0.9-17.3] and the median KREC was 111.9 [Q1-Q3: 29.3-339.28]. According to the results of the study, we noted statistically significant differences in TREC and KREC indices between all patients with malignancies and healthy individuals (p0.001, p=0.001). Analysis of TREC and KREC indices in patients with malignancies of various localizations (breast cancer, ovarian cancer, lung cancer, colorectal cancer, skin melanoma, lymphomas) in comparison with healthy individuals statistically significant differences in TREC level were noted (p=0.001, p0.001). When analyzing the KREC level in the studied groups, statistically significant differences in patients with ovarian malignancies (p0.001), lymphoma (p0.001), colorectal cancer (p=0.001) and melanoma (p=0.039) in comparison with healthy individuals were obtained. When comparing groups pairwise, it was found that TREC level in patients with malignancies in the age group of 25–44 years was significantly higher than in the age group of 45–60 years (p=0.03); TREC level in the age group of 25–44 years was significantly higher than in the age group of persons over 60 years (p0.001); TREC level in the age group of 45–60 years was significantly higher than in the age group over 60 years (p0.001). Statistically significant differences of KREC level in the studied patients with malignancies depending on the age group were not established (p=0.16), there were no age differences of groups by KREC level. Conclusion. The results demonstrate a significant decrease in TREC and KREC levels in patients with malignancies compared to healthy individuals. The study of TREC and KREC excision circles in peripheral blood is one of the promising approaches for the immunological evaluation of cancer patients.

INTRODUCTION. The development of malignant neoplasms is associated with changes in the expression of small non-coding RNAs (miRNAs). This emphasises the need for research into the development of miRNA-targeted inhibitors as a promising approach to cancer treatment.AIM. This study aimed to compare current strategies for suppressing the functional activity of tumour-associated miRNAs based on the use of therapeutic nucleic acids and to determine the application potential of these strategies.DISCUSSION. This study analysed known oligonucleotide-based miRNA inhibitors with different mechanisms of action. Based on their mechanism of action, miRNA-targeted inhibitors can be classified into two groups. The first group of miRNA-targeted inhibitors exhibits an indirect inhibitory effect, either by blocking functional connections between miRNAs and specific mRNA targets through the use of miRNA-masking oligonucleotides or by introducing mutations into miRNA genes and disrupting gene biosynthesis processes through the use of the CRISPR/Cas system. Despite their relatively high biological potential, these strategies are mostly used as search tools to study miRNA functional roles and molecular interactions in carcinogenesis. The second group of oligonucleotide constructs interacts with miRNA targets directly, which leads to steric blocking or degradation of oncogenic microRNAs. These miRNA-binding oligonucleotide constructs come in a variety of structural variants, including miRNA sponges, RNA zippers, antisense oligonucleotides, and miRNases, which demonstrate high therapeutic potential in vitro and in vivo.CONCLUSION. The described analysis of the biological properties, therapeutic potential, and key advantages of the developed miRNA-targeted oligonucleotide constructs helps outline the areas for their potential practical application in cancer treatment.

Alzheimer’s disease affects an average of 5 % of the population with a significant increase in prevalence with age, suggesting that the same mechanisms that underlie aging may influence this pathology. Investigation of these mechanisms is promising for effective methods of treatment and prevention of the disease. Possible participants in these mechanisms are transposons, which serve as drivers of epigenetic regulation, since they form species-specific distributions of non-coding RNA genes in genomes in evolution. Study of miRNA involvement in Alzheimer’s disease pathogenesis is relevant, since the associations of protein-coding genes (APOE4, ABCA7, BIN1, CLU, CR1, PICALM, TREM2) with the disease revealed as a result of GWAS make it difficult to explain its complex pathogenesis. Specific expression changes of many genes were found in different brain parts of Alzheimer’s patients, which may be due to global regulatory changes under the influence of transposons. Experimental and clinical studies have shown pathological activation of retroelements in Alzheimer’s disease. Our analysis of scientific literature in accordance with MDTE DB revealed 28 miRNAs derived from transposons (17 from LINE, 5 from SINE, 4 from HERV, 2 from DNA transposons), the expression of which specifically changes in this disease (decreases in 17 and increases in 11 microRNA). Expression of 13 out of 28 miRNAs (miR-151a, -192, -211, -28, -31, -320c, -335, -340, -378a, -511, -576, -708, -885) also changes with aging and cancer development, which indicates the presence of possible common pathogenetic mechanisms. Most of these miRNAs originated from LINE retroelements, the pathological activation of which is associated with aging, carcinogenesis, and Alzheimer’s disease, which supports the hypothesis that these three processes are based on the primary dysregulation of transposons that serve as drivers of epigenetic regulation of gene expression in ontogeny.

Markers for identification of ER+/PR breast cancer (BC) risks and conversion of ER+/ER+ to ER-/PR- tumors are necessary for effective prevention and therapy of BC by the selective ER – modificators. Purpose – To reveal the proposed associations of gene polymorphisms of ESR1 and ESR2 and antiidiotypic antibodies to estradiol (IgG2-E2) with ER+/PR+ BC risk and conversion of ER+/PR+ to ER-/PR- tumors and to study the interrelations between gene variants of ESR and IgG2-E2 in healthy women and BC patients. Polymorphic loci of ESR1 (rs2234693) and ESR2 (rs4986938) were studied by the real time PCR in 370 healthy women and 1169 BC patients. Tumor tissues ER and PR were detected by the standard immunohistochemical methods. Serum IgG2-E2 were studied using non-competitive enzyme immuno-assay. TT, TC and CC genotypes of ESR1 were revealed with the equal frequency in healthy women and BC patients I stage. Homozygotes GG of ESR2 were detected rarely, but AA frequently in BC patients with ER+/PR+ tumors at the I stage, than in healthy women женщин (44.0% and 14.2% vs 52.7 and 8.4%, respectively; p=0.005). The low levels of IgG2-ES were revealed more rarely but high levels more frequently in BC patients with ER+/PR+ tumors at the I stage, that in healthy donors (39.8% and 60.2% vs 58.0% and 42.0%, respectively; p=0.0002). Decreasing of ER+/PR+ tumors proportion and corresponding increasing of ER-/PR- tumors from I stage to II–IV stages (71.7% to 58.9% and 13.9% to 23.1%; p=0.006) were revealed in TC heterozygotes of ESR1 only. The same conversion of ER+/PR+ tumors to ER-/PR- were detected in GG homozygotes of ESR2 (p=0.004). There have been the similar ER/PR transformation in BC patients with high IgG2-E2 levels (74.7% to 57.6% and 11.3%, to 25.0%, respectively, p

Hormonal-induced changes in the breast occur due to both endogenous and exogenous sex hormones. For two decades, the safety of hormonal contraceptives (HC) in terms of their effect on breast tissue has been discussed in the literature. The pleiotropic effect of the components in the combined HC, on the one hand, prevents unwanted pregnancy; on the other hand, they help to maintain good health of women of childbearing age due to a wide range of non-contraceptive effects (eliminating hyperandrogenism manifestations, reducing the pain severity during menstruation and the menstrual blood loss, the risk of recurrence of functional ovarian cysts, oncoprotective effect due to reducing the risk of ovarian, endometrial, colorectal, pancreatic, and lung cancer). However, according to epidemiological studies, in addition to the beneficial effects, there are risks that require further study, including the controversial impact of HC on the oncogenesis and progression of breast cancer. In addition, some young women with breast cancer experience induced menopause after antitumor treatment. However, amenorrhea is not a marker for complete disabling of ovarian function, and pregnancy is associated with a risk of disease recurrence or progression. Therefore, in each case, it is necessary to determine the need for an effective and safe method of contraception.

Purpose. The aim of the review is to analyze the modern data on the molecular mechanisms of stomach and intestinal carcinogenesis, which can be the basis for managing of malignant stomach and intestine neoplasms mortality risks’ reduction. Materials and methods. The review includes data from foreign and domestic studies published in the electronic bibliographic databases PubMed, Cyberleninka, Elibrary over the past 10 years. Results. It is given the analysis of Wnt and β-catenin gene family role in the pathogenesis of stomach and colon malignant tumors and the carcinogenic potential of Helicobacter pylori in gastric cancer, as well as the driver bacteria contributing to the development of colon cancer. Conclusion. Stomach cancer and colon cancer are heterogeneous diseases with diverse molecular and histological subtypes, having both similarities and differences in the patterns of cancer promotion. Progress in transparency genesis of these diseases is associated with an understanding of cytotoxic and genotoxic effects, oxidative stress and chronic inflammation mechanisms.

Fusobacterium nucleatum is a component of the oral microflora, and in clinical practice it is associated primarily with periodontal diseases. Since 2011, the scientific community has confirmed the association of F. nucleatum with colorectal cancer (CRC) by seeding it from tumor tissue samples. Research has led to the discovery of mechanisms by which this bacterium may contribute to the development, metastasis of CRC and chemoresistance. With the help of its adhesion proteins (FadA and Fap2) F. nucleatum specifically attaches to colorectal carcinoma cells. Following invasion, F. nucleatum induces inflammation, activates β-catenin signaling, and creates a favorable microenvironment for tumor growth and development. Recently, the role of F. nucleatum in other types of oncological pathology, such as oral cavity cancer, head and neck cancer, gastric cancer, esophageal cancer, pancreatic cancer, cervical cancer and breast cancer, has been confirmed. Understanding the mechanisms of association of F. nucleatum with oncological diseases will help to find new approaches in the treatment, prevention and diagnosis of cancer. Thus, further studies of the correlation between F. nucleatum and carcinogenesis are needed, using a multidisciplinary approach and physicians from other specialties.

The review presents information on the role of hepatitis B virus (Hepadnaviridae: Orthohepadnavirus: Hepatitis B virus) (HBV) X gene and the protein it encodes (X protein) in the pathogenesis of viral hepatitis B. The evolution of HBV from primordial to the modern version of hepadnaviruses (Hepadnaviridae), is outlined as a process that began about 407 million years ago and continues to the present. The results of scientific works of foreign researchers on the variety of the influence of X protein on the infectious process and its role in the mechanisms of carcinogenesis are summarized. The differences in the effect of the X protein on the course of the disease in patients of different ethnic groups with regard to HBV genotypes are described. The significance of determining the genetic variability of X gene as a fundamental characteristic of the virus that has significance for the assessment of risks of hepatocellular carcinoma (HCC) spread among the population of the Russian Federation is discussed.

An interaction between decreasing host anti-infective defense due to long-term invasion with Opisthorchis felineus in the hepatobiliary system, duct bile colonization by microflora and revealing the endogenous mutagenesis (carcinogenesis) factor in bile — secondary bile acids — is considered in the article. The role of organism genotype in pathogen-related immune response to Opisthorchis felineus trematode and helminth development in the hepatobiliary system has been shown. The role of dysregulated mechanisms of tissue homeostasis in induction of compensatory chronic homeostatic proliferation and somatic cell oncogenesis is discussed. The study results evidence that disturbed functioning of regulatory T cells, inhibition of the NK cell effector function and very high functional activity of memory B cells are of great importance in imbalanced host immunobiological reactivity, caused by chronic opistorchis invasion. Decreased host anti-infective protection causes intrahepatic bile duct infection with different bacterial species. Presence of secondary bile acids in hepatobiliary system was associated with biliary bacterial strains inhabiting intestinal tract: Proteus vulgaris, Proteus mirabilis, Citrobacter freundii, Bacteroides alcaligues faecalis, Clostridium, Streptococcus faecalis, Еscherichia coli — gut microflora agents. Participation of microbiota in bile acid biotransformation immediately in the duct bile has been confirmed in experiments in vitro. Experimental methods on Drosophila melanogaster and Salmonella typhimurium strains: TA100, TA98 allowed to find out that bile from chronic opistorchiasis patients exerts higher mutagenic activity compared to control groups. Mutational events in somatic and bacterial cells depend on the presence of secondary bile acids (deoxycholic, lithocholic) in duct bile, as well as the level of total bile acid concentration. The study data confirm the concept by Professor A.A. Shain about the presence of endogenous risk factor for developing primary cholangiocellular liver cancer such as secondary bile acids in the bile of chronic opistorchiasis patients. A concept of cholangiocarcinogenesis, based on mutational events, is added up with disturbance of generative cycle in tissue cells and their differentiation due to decreased chalone factor activity, as well as sensitivity threshold to it. Level of investigation and understanding of mechanisms underlying cholangiocarcinogenesis during chronic opisthorchis invasion will allow to develop pathogenetic approaches to correct homeostasis regulation and prevention of cholangiocarcinomas.

Analysis of scientific literature data has revealed several ways in which retrotransposons, when activated, are involved in carcinogenesis. First, retroelements can encode oncogenic proteins. For example, the Np9 protein is translated from HERV-K endogenous retrovirus transcript. Second, retroelements are used as alternative promoters of protooncogenes. Accordingly, their activation contributes to the enhanced expression of oncogenes (e.g. CSF1R, IRF5, MET, RAB3IP, CHRM3). Third, retroelements are located in the introns of some genes, and upon their activation, they form chimeric transcripts, such as LTR2-FABP7, LTR-ALK, LTR-ERBB4, LINE1-MET, which have pronounced oncogenic activity. Fourth, retroelements are transposed into tumor suppressor genes (e.g. APC, NF1, MSH2, PTEN, RB1, TSC2, STK11, VHL) and inactivate them, which is associated with the presence of hot spots of insertional mutagenesis in them. As a result, the growth of tumors and the survival of their cells are stimulated. It is important to note that protein products of tumor suppressor genes, such as TP53, RB1, VHL, BRCA1, ATM, are characterized by the ability to inhibit the activity of retroelements. Accordingly, when even one oncosuppressive gene is inactivated, a kind of "vicious circle" can be triggered when the control of expression of retroelements is weakened. The latter, in turn, inactivate other tumor suppressors containing hot spots of insertional mutagenesis. This stimulates new pathways of carcinogenesis and the production of oncogenes associated with transposons. Thus, it is possible to explain in a new way the mechanisms of tumor formation in hereditary tumor syndromes. This is due to the fact that the weakening of the function of an oncosuppressor in a germinal heterozygous mutation may be sufficient to trigger a vicious circle involving retroelements, oncogenes and other oncosuppressors. Similar mechanisms are likely for sporadic malignant tumors. However, the initiating event in them can be the direct activation of transposons under the influence of stressors, chemical and physical carcinogens. In addition to the events described, activation of retroelements causes genomic instability, which contributes to complex genomic rearrangements often observed in malignant tumors. MicroRNAs and long noncoding RNAs, the sources of which are retroelements, also play an important role in the evolution of tumors. Their study is promising for the development of targeted therapy for neoplasms.

For all tumors, regardless of type and tissue, there are a number of common features. These include high proliferative activity, disturbances in the mechanisms of apoptosis and "invisibility" for the cells of the immune system. At the basis of all these disorders lies a malfunction in the interaction between signaling proteins inside the cell, due to a violation of the expression of genes responsible for their synthesis. The aim of the review is to study the molecular biological mechanisms of carcinogenesis, characteristics and features of tumor cells that affect the development of the disease, progression, drug resistance and clinical results and the possibilities of targeted therapy of oncological diseases. Material and methods. The search for literature sources was carried out using PubMed, CyberLeninka, eLibrary, Google Scholar databases; the search depth was 15 years. Results. Recent works have shown the evolution of views on the classification of tumors from the point of view of the mechanisms of damage to the processes of cellular regulation and histogenesis, as well as the development of the modern theory of carcinogenesis, ideas about the mechanisms of development of tumor diseases and the prospects of modern therapies. Conclusion. The study of molecular biological mechanisms of carcinogenesis, characteristics and features of tumor cells is not only fundamental, but also of applied importance in order to predict the development of the disease, progression, drug resistance, clinical results and the possibilities of targeted therapy.

Article presents current data on the contribution of the human microbiota to the development of oncological conditions, microbial impact on cell transformation, influence on chemotherapy outcome. Brief description of the methods used for studying microbiota in carcinogenesis as well as prospects of creating non-invasive diagnostic tools is given.

Aim. A study of atrophic gastritis severity and rate in patients with gastric polyps (GP).Materials and methods. The study enrolled 61 patients with hyperplastic (HGP) and 41 — with adenomatous GP (AGP). All patients had 24-h gastric pH-metry, control of the pepsinogen I, II and gastrin-17 levels, in addition to a general clinical, endoscopic, histological examination and testing for Helicobacter pylori.Results. GP patients had benign manifestations prevailed with epigastric heaviness and overflow, and a scarce history of H. pylori testing at no control of rendered eradication therapy. A symptomatic proton pump inhibitor treatment in GP was either prescribed or voluntary. Focal atrophic gastritis in endoscopy was revealed in 12 (19.7 %) HGP and 16 (39.0 %) AGP patients, diffused atrophic gastritis — in 49 (80.3 %) HGP and 25 (60.9 %) AGP patients. Low-grade chronic gastritis in histology prevailed in HGP, moderate — in AGP, and severe — in 21.9 % cases. Moderate (27.9 %) to severe (65.6 %) atrophy of gastric mucosa was registered in HGP, with 53.7 and 39.0 % respective AGP cases. Polyp dysplasia was detected in 20 % HGP and 75.6 % AGP cases. Pepsinogen I H. pylori-positive were 52.5 % HGP and 70.7 % AGP cases.Conclusion. A largely similar aetiopathogenesis of gastric polyps and chronic atrophic gastritis warrants the H. pylori diagnosis and a more detailed patient control for chronic gastritis grading and staging, functional insufficiency of gastric mucosa and the severity of hyperplastic and dysplastic change. The H. pylori eradication, in contrast to anti-secretory therapy, allows the containment of chronic gastritis and is a critical measure in gastric cancer prevention.

Despite significant advances in the diagnosis and treatment of oncopathology, the main epidemic indicators have a negative trend.Based on the above, a very relevant topic is the development of experimental models of carcinogenesis. The importance of scientific work in this area is increasing because in experimental conditions it is better to test new methods, diagnostics and treatment. Thus, it becomes possible to study the peculiarities of the pathogenesis of any tumor at different stages.The purpose of the work – to study and demonstrate the strengths and weaknesses of the main experimental models of carcinogenesis for further selection of the most appropriate.Results The main directions of carcinogenesis modeling are presented in the article. Initially, the problem was justified. The next step is described in chronological order of using the models.Of course, the achievements of clinical and experimental oncology played an important role in the emergence of models. Thus, the first model was the effect of physical and chemical carcinogens on a laboratory animal. The latest achievement of experimental oncology is the use of stem cells in combination with genetic engineering.No less important is the fact of comparing experimental models. We present the strengths and weaknesses of all these models.Conclusions1. To date, there are a large number of experimental models of carcinogenesis.2. When planning a study, you need to calculate all the goals to be achieved and select the appropriate model.3. The most effective and common model for ascites ovarian tumor is the transplantation of atypical cells to laboratory animals.

Gastric cancer is currently one of the most prevalent malignancies worldwide with a high mortality rate. Helicobacter pylori (H. pylori) infection significantly contributes to the onset and progression of gastric cancer mainly due to the induction of chronic inflammatory responses. The pathogenicity of H. pylori is associated with a vast number of virulence factors among which cytotoxin-associated gene A (CagA) plays a crucial role. We conducted a literature review of PubMed, Web of Science, and Scopus on September 1st, 2021. There were no limits regarding the year and the language of publication. Articles included in this review concerned human and animal studies. The following search string was applied during the search: (gastric cancer) AND (epithelial-mesenchymal transition) AND (Helicobacter pylori) AND (cytotoxin-associated gene A). The final analysis included 135 articles independently reviewed by the authors. H. pylori CagA-positive strains seem to be more virulent compared to the CagA-negative strains. CagA pathogenicity includes the increased secretion of pro-inflammatory cytokines, induction of cancer stem cell-like properties, apoptosis prevention, or overactivation of particular oncogenic pathways. H. pylori might induce epithelial-mesenchymal transition (EMT) via numerous pathways, among which CagA-related pathogenicity is considered to be of high significance. Mechanisms associated with CagA action are involved in the maintenance of chronic H. pylori infection, subsequent EMT induction, and further onset and progression of gastric cancer. Because of a huge number of H. pylori strains with different virulence mechanisms, the clinical outcome of patients is also associated with the particular type of strain that infected a patient.

Introduction:One of the main characteristics of cancer is uncontrolled cell proliferation as well as loss of cells adhesion in the case of metastases. Cadherins and catenins are the molecules responsible for cell-to-cell interaction. Together, they form a complex called ECCU (E-cadherin/catenin complex) which maintains the proper tissue structure. However, an impairment in its functioning can result in many adverse health effects, such as cancer promotion. Purpose: To evaluate the potential role of ECCU complex in carcinogenesis. Materials and methods: We performed the database research using PubMed, Springer Link and ResearchGate and we made review and meta-analysis of relevant studies. We searched for studies analyzing the relationship between ECCU complex and carcinomas development. Results: ECCU takes part in many cell processes and pathways, such as Wnt/Wingless‐signaling pathway or EMT/MET processes. It interacts with various molecules, for instance p27 protein or transcription factors. Aberrations in the expression of ECCU components is related to carcinoma promotion, shorter survival rate of patients and poor differentiation of the tumor. Conclusions: A role of the ECCU complex is complicated, however there is a clear correlation between loss of cell adhesion and carcinoma promotion and progression. The complex can be a possible target of anti-cancer therapy in the future; it is also under investigations as a marker of the disease, however it is questionable.

Background: Barrett's esophagus (BE) is a precan-cerous disease of the esophagus. The risk of adenocarcinoma in BE patients increases with the extension of segment length and with the presence of dysplasia. Columnar-lined esophagus (CLE) devoid goblet cells is also associated with dysplasia and adenocarcinoma, however, with a lower risk. Aim: To perform clinical and morphological analysis of patients with BE with goblet cells and CLE devoid goblet cells on the presence or absence of dysplasia. Materials and methods: This prospective clinical morphological study included 78 patients with columnar-lined esophagus at EGDS, among them 20 patients with a long segment, 58 patients with a short segment. Biopsy specimens from the CLE area of the distal part of the esophagus were stained by hematoxylin and eosin and standard PAS-reaction with Alcian blue. Histological examination showed BE with goblet cells in 49 patients and CLE devoid goblet cells in 29 patients. In those with BE, the morphometric analysis of the goblet cells density was performed and the number of the affected crypts was counted in dysplastic fragments. Results: In the short segment group, the male to female ratio was ~ 1:1.1, and CLE devoid goblet cells was found in 53% of cases (27/58 patients), and BE with goblet cells in 57% of cases (31/58 patients). In the long segment group, the male to female ratio was ~ 2.3:1, along with predominance of BE with goblet cells cases (18/20 patients, 90%) and high density of goblet cells (11/18 patients, 61%). The rates of goblet cells detection increased with the extension of the segment length (p < 0.05). The relative goblet cells density in the patients with the long BE segment was also significantly higher than in the short segment group (p < 0.001). Advanced inflammatory infiltration was found in 22 of 58 (38%) cases with the short segment and in 13 of 20 patients with the long one (65%, p = 0.012). The rates of erosion in the long segment group were 1.62-fold higher and ulcerations 3.87-fold higher (p = 0.014). Esophageal dysplasia was identified in 10 of 20 cases (50%) with the long segment and in 2 of 58 cases (3.4%) with the short segment. In 10 of 12 cases (83.3%) dysplasia was multifocal and involved from 2 to 10 crypts (in total, up to 25 crypts). Conclusion: The long segment of metaplasia was associated with higher rates of active chronic esophagitis, higher presence of goblet cells and their higher density. Dysplasia was found in 10 patients with three and more risk factors of progression (male gender, long segment, hiatal hernia, etc.). In most cases, the biopsy samples showed multiple foci of dysplasia.

Aim. To analyze and systematize the available information on pathogenetic mechanisms of hormonal carcinogenesis. Materials and methods. The review includes data from foreign articles published in PubMed and Medline and national works posted on elibrary.ru over the past 20 years. Results. Currently, the term estrogen is often used in the context of hormonal carcinogenesis. According to most researchers, it should not fit into the narrow framework of receptor-mediated proliferation induced by estrogens in target tissues. The concept of estrobiome as a combination of all mechanisms providing the realization of estrogen effects should include not only hormones and native receptors themselves, but also the enzymes involved in their synthesis, estrogen metabolites, intestinal microbiota, as well as genetic and epigenetic factors. Conclusions. When analyzing cancer risk, it is necessary to comprehensively assess contributing factors and hormonal-metabolic preconditions for neoplastic process.

One of the most outstanding scientific achievements in the thrombolysis is the development and administration of fibrinolysin - the first Soviet drug that lyses blood clots. Intracoronary administration of fibrinolysin reduced the mortality of patients with myocardial infarction by almost 20%. For his work in this field Yevgeny Chazov was awarded the Lenin Prize in 1982. Over the next decades, under his leadership, the Cardiology Center established scientific and clinical laboratories that created new generations of drugs based on fibrinolytics for treating patients with myocardial infarction, restoration of blood flow in ischemic tissue, and also studying the mechanisms of remodeling of blood vessels involving the fibrinolysis system. It have been found new mechanisms of regulation of the navigation of blood vessels and nerves growth, tumor growth and its metastasis with the participation of the fibrinolysis system proteins. The review reports the role of the fibrinolysis system in the thrombolysis, blood vessels growth and remodeling, neurogenesis, carcinogenesis and fibrosis. The article is dedicated to the 90th anniversary of academician E.I. Chazov.

Summary Introduction and objective: Cancer arises from genetic and epigenetic changes in the cell. Indication of the direct causes of cancer is no doubt very difficult, because the process of carcinogenesis is a multi-level and multi-stage. Knowledge of existing threats to health is a determinant in making everyday decisions that are crucial in minimizing the risk for precancerous and cancerous. Featured Review article is only an outline of selected factors participate in the induction of neoplastic process. Its aim is to present the concept and the process of carcinogenesis, and to discuss the participation of selected factors in the induction of neoplastic lesions. Description of knowledge: Preiniciation is a period in which the carcinogenic effect on normal cells. Initiation is related to the appearance of the first permanent changes in the genetic material of the cell. The promotion is the stage in which the diseased cells grow and multiply. However, in the progression of metastasis occurs it. Factors that are surrounded by human impact on the integrity of the genetic material. Many of them have been scientifically proven effect mutogenne and carcinogenic. Conclusions:The effects of interactions of carcinogens accumulate in different time intervals. Carcinogens interact with DNA, causing deterioration or change in its structure. They can also cause changes in gene expression. Carcinogenic for a human body may be the same ingredients, food products and substances in food preservatives. Some viruses can be oncogenic due to the integration of the viral genome into the host genome in the vicinity of proto-oncogenes. Exposure to heavy metals and their metabolites contribute to DNA damage.

Introduction and objective: Free radicals (ROS), affect the course of each step of the process of carcinogenesis. Antioxidants that interact with ROS inactivates them, resulting in a positive effect both in preventing and inhibiting the progression of cancer. Vitamins such as A, C, E and D have anticancer properties. The article gives an overview of the problems of comp contribution of each vitamin in the chemoprevention of cancer. Its purpose is to present some antioxidants for its potential anti-tumor and to provide modifications to their effect on the carcinogenesis process. Description of knowledge: Vitamin A inhibits inter alia, lipid peroxidation and influences the growth and differentiation of epithelial cells to prevent neoplastic transformation. Vitamin E inhibits inter alia, angiogenesis, growth and proliferation of diseased cells. It also has the ability to stop the cell cycle. It prevents the formation of carcinogenic nitrosamines. Vitamin D inhibitor of vascular endothelial growth factor, and factors stimulating cell proliferation. Suppressive affects COX-2 enzyme. Increases the synthesis of E-cadherin. Vitamin C contributes to the proper functioning of the immune system by stimulating the activity of B and T lymphocytes is an electron donor for protecting cell components against oxidation. Stimulates cells to produce hyaluronidase inhibitor. Induces the synthesis of proteins p73 and MLH1. Conclusions: Imbalance redox system can lead to neoplastic transformation. Taking antioxidant supplements is associated with the risk of delivering them in too large a dose. Consequently, there is a support of the oxidation processes. The best way to protect against cancer and support cancer therapy is to provide antioxidants in their natural form, ie in the form of fresh vegetables and fruits.

Previous studies reported some associations between class A antibodies specific for benzo[a]pyrene (IgA-Bp), estradiol (IgA-Es) and progesterone (IgA-Pg) and breast cancer (BC) in women like as with lung cancer (LC) in men. It was suggested that IgA-Bp and IgA-Es may stimulate tumor initiation and promotion, whereas IgA-Pg may inhibit the in vivo human carcinogenesis.The purpose of this study was to identify the suggested associations of such immunological imbalance with BC and LC in postmenopausal women.The serum A-class antibodies specific to benzo[a]pyrene, estradiol and progesterone (IgA-Bp, IgA-Es, IgA- Pg) were studied in 335 healthy women, 824 breast cancer (BC) patients and 127 cases of lung cancer (LC) by means of non-competitive solid phase immunoassay. The following results were obtained: Increased ratio of IgA-Bp and IgA-Es amounts exceeding the IgA-Pg levels was associated with a higher risk of breast cancer (OR = 2.8 and 2.4 respectively, p < 0.0001), and higher risk of LC (OR = 2.9 and 2.8, respectively, p < 0.0001). Conversely, the OR values decreased to 0.3-0.4 for BC and LC if IgA-Pg levels were higher than IgA-Bp and IgA-Es levels (p < 0.0001). These findings confirm the hypothesis that IgA-Bp and IgA-Es are capable to stimulate, and IgA-Pg, to inhibit the BC and LC occurrence n postmenopausal women. The balance between IgA-Bp and IgA-Es, on the one hand, and IgA-Pg, on the other hand, is much more important than individual contents of these antibodies.In conclusion, the phenomenon of “immunological interference” is revealed, i.e., the mutual enhancement of IgA-Bp and IgA-Es effects, thus, probably, stimulating the initial and subsequent events of carcinogenesis initiation and promotion, with a weak anticancer effect of IgA-Pg, and by weakening the mutual procarcinogenic effects of IgA-Bp and IgA-Es by the marked effect of IgA-Pg.

Oral cancer is an aggressive and rapidly progressive disease. The oral cavity is home to over 700 species of microorganisms that regulate metabolism, immune function, and health. There are three types of mechanisms by which bacteria may participate in carcinogenesis. First, bacteria cause chronic inflammation, which stimulates the production of cytokines, including interleukins, interferons, and tumor necrosis factor. Second, bacteria can interact directly with host cells by secreting toxins or by binding to membrane receptors. Finally, the production of metabolites by bacteria may also contribute to carcinogenesis. The importance of the bacteria level and composition in the transition of oral precancerous lesions to cancer has been demonstrated. The relationships of changes in microbiome composition with smoking, inflammation in healthy individuals, as well as with the development of oral cancer in patients, have been studied.

Significant progress in understanding the mechanisms of carcinogenesis is associated with the discovery of tumor suppressor genes (or antioncogenes). It is known that in the human population, the number of normally functioning suppressor genes varies in different individuals at birth. The aim of the study was to assess the probability of cancer development in an individual with a different initial number of undamaged normally functioning antioncogenes. On the basis of the probabilistic mathematical model of carcinogenesis, the most probable age of cancer development depending on the number of intact antioncogenes was assessed. As a result of the studies, the probability of cancer development depending on the age of the patient is estimated. The dependence of the probability of cancer development in an individual on the number of undamaged antioncogenes is also investigated. The analysis of the significance of the number of tumor suppressor genes, the damage of which may be the cause of initiation of cell malignancy, has been carried out.

Previous studies have revealed associations of antibodies, specific to chemical carcinogens and steroid hormones with lung cancer in men. However, the mechanisms of their formation and action were remained unclear. In particular, the relationships between antibodies and gene polymorphisms of cytokines were un- known. The purpose of this study was to identify possible associations between occurrence of A class antibodies, specific to benzo[a]pyrene, estradiol and progesterone (IgA-Bp, IgA-Es and IgA-Pg), and frequency of genetic polymorphisms of IL1RN VNTR, IL1В (rs1143634, rs16944), IL4 VNTR, IL6 (rs1800795), IL10 (rs1800896), TNFA (rs1800629, rs361525) genes in healthy male smokers and lung cancer patients.We have examined 381 men with non-small cell lung cancer and 158 apparently healthy donors without respiratory diseases. A non-competitive solid phase immunoassay of antibodies was performed. Analysis of polymorphic loci of IL1RN (VNTR, intron 2), IL4 (VNTR, intron 3) was performed by means of conventional PCR; IL1В (rs1143634, rs16944), IL6 (rs1800795) SNPs were detected by RFLP, and IL10 (rs1800896), TNFA (rs1800629, rs361525) genotyping was carried out with TaqMan Real-time PCR. Results of the study have shown that the proportion of cases with high level of IgA-Pg and low levels of both IgA-Bp and IgA-Es among the lung cancer patients was lower than in healthy men (OR = 0.31, p < 0.0001). Vice versa, the ratio of cases with high levels of both IgA-Bp and IgA-Es and low levels of IgA-Pg was higher in lung cancer patients (OR = 3.6, p < 0.0001). No relationships were revealed between the levels of antibodies, and rates of genetic polymorphisms for the studied cytokines in both groups of men. At the same time, the detected associations of IgA-Bp, IgA-Es and IgA-Pg with lung cancer proved to be significant only in carriers of certain cytokine genotypes, e.g., in AG IL10 heterozygotes (OR = 5.1, p < 0.0001).In conclusion, these results provide indirect evidence that IgA-Bp and IgA-Es could stimulate initiation and promotion of lung carcinogenesis. On the contrary, IgA-Pg could inhibit the promotion of carcinogenesis. Immunoassay of these antibodies combined with molecular biology studies of IL10 gene variants are recommended for the lung cancer risk assessment.

Antibodies against sex steroid hormones are known to modulate their serum concentration and inhibit experimental breast cancer (BC). Hence, these effects could be changed by according anti-idiotypic antibodies. However, relationships between antibodies and anti-idiotypic antibodies and BC in women are still poorly studied. The aim of this study was to identify possible associations between occurrence of antibodies against estradiol and progesterone (IgG-Es1and IgG-Pg1) and according antiidiotypic antibodies (IgG-Es2 and IgG-Pg2), and postmenopausal BC. Eighty-nine healthy women and 273 BC patients were examined. A non-competitive solid phase immunoassay for IgG-Es1 and IgG-Pg1 was performed using estradiol and progesterone conjugates with bovin serum albumin as antigens. Monoclonal antibodies against Es and Pg as antigens have been used for noncompetitive solid phase immunoassay of IgG-Es2 and IgG-Pg2. Results: absence of both IgG-Es1 and IgG-Pg1 was revealed in 53.9% of healthy donors and 41.0% of BC patients (p = 0.04; OR = 0.6). Presence of IgG-Es1 without IgG-Pg1, or IgG-Pg1 without IgG-Es1was detected for, respectively, 15.7% and 20.2% of healthy women, and in 10.3% and 7.7% of BC patients (p > 0.05). Simultaneous increase of both IgG-Es1 and IgG-Pg1 was revealed in 10.1% of healthy donors and in 41.0% of BC patients (p < 0.0001; OR = 5.3). Absence of a single antibogy (IgG-Es2 or IgG-Pg2) showed similar frequency in the groups under study. Simultaneous increase of both IgG-Es2 and IgG-Pg2 was detected in 52.8% of healthy women and 34.8% of BC patients (p = 0.03; OR = 0.4). Conclusion: We have first revealed an immunostimulating synergistic effect of antibodies against sex steroid hormones and immunoinhibitory synergistic effect of appropriate anti-idiotypic antibodies upon the postmenopausal breast cancer risk.

Activation of the growth factors pathways is involved in cell growth and proliferation and is associated with carcinogenesis. Many studies have shown an increase in blood growth factors concentrations after training. On the other hand, numerous organisations recommend physical activity in cancer therapy and prophylaxis. This two phenomena may actually cause confusion. The aim of this paper was to present findings on the significance of physical activity in course of neoplastic disease and dispel doubts concerning its role in cancer treatment.

The paper confirms long-time opisthorhis invasion role as a risk factor of host immune system reconstitution as well as an important factor in holangiocarcinomas development. It was shown that opisthorhosis invasion primal stage induce host immune system reconstitution. Host immune B-cells system is activated by metacercaria antigens, while the same antigens inhibits T-cells activity. Opisthorhis metabolites stimulate proliferative mithogen-induced T-cells acti vity. Chronic opisthorchis invasion leads to immune system disbalance. It means: decrease of specific and non-speci fic natural killers activity, number of high proliferative activity T-lymphocytes and the shift of regulatory T-cells subset to suppressors prevalence. At the same time specific as well as non-specific T-suppressors functional ability is very low. It was shown T-cells helper-amplifier activation. Despite of circulating B-cells decrease the antibody produced cells number is spleen increases significantly at the same time with circulating immune complexes accumulation. Even 3–6 month after dehelmintisation the immune system disbalance decreases but lefts. In addition, chronic opisthorhis invasion leads to the proliferative processes activation in ductal epithelium, liver, lymph nodes and in other organs which leads to cancer proliferation. According to the results obtained the opisthorhis infected patients needs to be immunocorrected before as well as after dehelmintisation for holangiocancerogenesis profylaxis.

TGR5 are G-protein-linked, membrane bile acids receptors that widely express in tissues of animals and humans. Namely tissue localization of TGR5 determines biological effects of activation of these receptors. This review focuses on the role of TGR5 as a new pharmacological target for the treatment of patients with metabolic syndrome, diabetes, obesity, atherosclerosis, liver disease and cancer processes.

Some genetic polymorphisms of CYP and GST enzymes metabolizing low-molecular weight xenobiotics may represent endogenous risk factors for carcinogenesis. However, possible relationships between the enzyme activities, amounts of carcinogen adducts and synthesis of anticarcinogen antibodies in humans (including cancer patients) are still poorly studied. The purpose of this study was to identify possible associations between occurrence of antibodies against benzo[a]pyrene, and frequency of genetic polymorphisms of CYP1A1*2A, CYP1A2*1F, GSTT1, GSTM1 in healthy men and in lung cancer patients. Materials and methods. We have examined 203 men with non-small cell lung cancer and 267 apparently healthy donors without respiratory diseases. A non-competitive solid phase immunoassay of antibodies to benzo[a]pyrene was performed. Analysis of polymorphic loci within CYP1A1 (rs4646903), CYP1A2 (rs762551), GSTP1 (rs1695, rs1138272) was performed by means of real-time PCR using TaqMan technology. Null-alleles of GSTM1 (del), GSTT1 (del) genes were detected by multiplex PCR with real-time fluorescent assay. Results. Among the lung cancer patients, the proportion of cases with a high level of IgG antibodies to benzo[a]pyrene in carriers of GSTT1+ and GSTM1+ in conjunction with the CYP1A2*1F C allele was significantly greater than in AA homozygotes CYP1A2*1F. The risk of lung cancer was increased to 5.5 in carriers of CYP1A2*1F C allele combined with GSTT1+ and GSTM1+ at high levels of IgG antibodies to benzo [a] pyrene. In healthy male donors, we have not found differences between the incidence of low and high levels of IgG anti-benzo[a]pyrene antibodies in the carriers of certain CYP1A1*2A, CYP1A2*1F, GSTT1 and GSTM1 genotypes. Conclusions. We have first reported a relationship between CYP1 and GST gene polymorphisms and specific immune response to chemical carcinogens in lung cancer patients. Immunoassays of IgG antibodies to benzo[a]pyrene combined with molecular biology studies of CYP1 and GST are recommended for the cancer risk assessment.

The article presents the review of contemporary concepts of tumor induction mechanisms applicable for neoplastic transformation, promotion and proliferation. The paper also contains an in-depth analysis of results of authors' own observations and study of immunological protection mechanisms of a significant number of patients diagnosed with oncopathologies of mammary and thyroid glands as well as adenocarcinoma of ascending colon. We have established common development patterns of T-cell and B-cell immunodeficiencies that are not influenced by location and proliferation of neoplastic tumors; the progress of such immunodeficincies, however, depends on regional metastasis development. Thus, we can conclude that insufficiency of immunological defense mechanisms leading to disruption of maligned cell elimination process is the primary pathogenic factor for metastatic tumor development.

In experimental models it was shown that the family of insulin-like growth factors (IGF), the main representative of which is IGF-1 exerts mitogenic, antiapoptotic and angiogenic activity. It is known that IGF-signaling pathway is involved in the activation cascade of the mitogen-activated protein kinases, resulting in the blocking of apoptosis. Clinical studies confirm the need for the involvement of IGF signaling pathway in the development and progression of ovarian cancer (OC).Subjects and methods. The study included 44 patients with ovarian cancer, 7 patients with borderline and 14 benign ovarian tumors. The ELISA analysis determined the content of insulin-like growth factors type 1 and 2 in tumor tissue and serum of patients with neoplasm of the ovary.Results. In the tissue of ovarian cancer content of IGF-1 were significantly lower than in the tissue of benign tumors. Serum levels of IGF-1 and IGF-2 correlated negatively with the prevalence of OC. Found direct correlation between levels of IGF-1 and IGF-2 in ovarian cancer tissue, and poor direct correlation between serum levels of IGF-1 and IGF-2. The median follow-up period was 14 months and the median time without recurrence was 13.5 months. It is established that two-year disease-free survival is reduced by 40% when low serum levels of IGF-I, and 30% at low levels of IGF-2. In patients with residual tumor size less than 1 cm with high serum levels of IGF-1 (87 ng/ml) two - year disease-free survival was 66.2%, and at low levels of IGF-1 - 25% (p=0.016).Conclusions. The levels of IGF-1 and IGF-2 in tumor tissue and serum in patients with ovarian cancer were decreased in the tumor process. Elevated levels of IGF-I can be considered as a factor of favorable prognosis in patients with ovarian cancer who underwent cytoreductive surgery with residual tumor of less than 1 cm.

Matrix metalloproteinase-7 (MMP-7) is able to cleave almost all the elements of the extracellular matrix. It is believed that due to its ability to degrade the basal membrane, it is involved in the processes of invasion, metastasis and neoangiogenesis. Vascular endothelium growth factor (VEGF) has demonstrated its role in tumor progression. Subjects and methods. The study included 65 patients with tumors of the ovary, 44 cancer was diagnosed. Using enzyme-linked immunosorbent assay we determined the content of MMP-7 and VEGF in the serum and tumor tissue in patients with tumors of the ovary. Results. Serum levels of MMP-7 and VEGF are positively correlated with the prevalence of ovarian cancer (OC). In the tissue of adenocarcinoma of the ovary are determined higher levels of MMP-7 and VEGF than in tissue of benign tumors. In the tumor tissue of OC registered positive correlation between VEGF and MMP-7 (r=0.6); p=0.0001. The period of observation did not exceed 2 years from the start of treatment, median follow-up time was 14 months. Only the size of residual tumor after cytoreductive surgery is significantly associated with long-term results. Communication levels of MMP-7 with long-term results of treatment of OC patients is not established. Two-year disease-free survival in patients with baseline serum VEGF value of more than 440 PG/ml was 24%, less than 440 PG/ml - 55%. Conclusions. The levels of MMP-7 and VEGF in tumor tissue and serum in patients with OC increase with the prevalence and aggressiveness of tumor process. Elevated levels of VEGF can be considered as a factor of poor prognosis in patients with OC.

5-Methyl-2'-deoxycytidine (mC) at CpG sites plays a key role in the epigenetic gene regulation, cell differentiation, and carcinogenesis. Despite the importance of mC for normal cell function, CpG dinucleotides are known as mutagenesis hotspots. Deamination of mC yields T, causing C→T transitions. However, several recent studies demonstrated the effect of epigenetic modifications of C on the fidelity and efficiency of DNA polymerases and excision repair enzymes. The review summarizes the available data that indicate the existence of deamination-independent mechanisms of mutagenesis at CpG sites.

Bagmut I. Yu., Zharova N. V., Popova T. M., Zhukov V. I., Stetsenko S. O. Express experimental evalution of mutagenic activity of complex phoshorus-containing organic mixtures = Експрес-експериментальна оцінка мутагенної активності складних фосфоровмісних органічних сумішей = Экспресс-экспериментальная оценка мутагенной активности сложных фосфоросодержащих органических смесей Journal of Education, Health and Sport. 2016;6(10):443-454. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.164190 http://ojs.ukw.edu.pl/index.php/johs/article/view/3971 The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part B item 755 (23.12.2015). 755 Journal of Education, Health and Sport eISSN 2391-8306 7 © The Author (s) 2016; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 02.09.2016. Revised 24.09.2016. Accepted: 30.10.2016. UDK 579.695 EXPRESS EXPERIMENTAL EVALUATION OF MUTAGENIC ACTIVITY OF COMPLEX PHOSPHORUS-CONTAINING ORGANIC MIXTURES I. Yu. Bagmut, N. V. Zharova, T. M. Popova, V. I. Zhukov, *S. O. Stetsenko Kharkiv Medical Academy of Postgraduate Education; *Kharkiv National Medical University Summary Researching the mutagenic activity of organic phosphorus-containing mixtures of Esherichia Coli bacteria strain trp A 223 and the continuous cells culture of murine myeloma X63 also detected the presence of weak mutagenic properties in this group of xenobiotics. The concentrations of all compounds 400 and 1000 mg/l have bacteriostatic effect, and their lower concentrations in the range from 10 to 80 mg/l stimulate the mutagenic activity. Phosphorus-containing organic compounds can inhibit the synthesis of proteins, RNA and DNA in cell culture Vero depending on the concentration. Key words: xenobiotics, carcinogenesis, mutagenesis, atherogenesis, suppression of immune deficiency, reproductive function, Esherichia Coli, cells culture of murine myeloma X63. ЕКСПРЕС-ЕКСПЕРИМЕНТАЛЬНА ОЦІНКА МУТАГЕННОЇ АКТИВНОСТІ СКЛАДНИХ ФОСФОРОВМІСНИХ ОРГАНІЧНИХ СУМІШЕЙ І. Ю. Багмут, Н. В. Жарова, Т. М. Попова, В. І. Жуков, * С. О. Стеценко Харківська медична академія післядипломної освіти; *Харківський національний медичний університет, м. Харків Резюме Дослідження мутагенної активності фосфорвмісних органічних сумішей на бактеріях Esherichia Coli штам trp A 223 і перевиваємій культурі клітин мишачої мієломи Х63, виявили наявність слабких мутагенних властивостей досліджуваних ксенобіотиків. Всі сполуки в концентраціях 400 і 1000 мг/л володіють бактеріостатичним ефектом, а в більш низьких концентраціях в діапазоні від 10 до 80 мг/л вони стимулюють мутагенну активність. В залежності від концентрації, фосфорвмісні органічні сполуки здатні пригнічувати синтез білків, РНК і ДНК в культурі клітин Vero. Ключові слова: ксенобіотики, канцерогенез, мутагенез, атерогенез, пригнічення імунологічної недостатності, репродуктивна функція, бактерії Esherichia Coli, клітини мишачої мієломи Х63. ЭКСПРЕСС-ЭКСПЕРИМЕНТАЛЬНАЯ ОЦЕНКА МУТАГЕННОЙ АКТИВНОСТИ СЛОЖНЫХ ФОСФОРОСОДЕРЖАЩИХ ОРГАНІЧЕСКИХ СМЕСЕЙ И. Ю. Багмут, Н. В. Жарова, Т. М. Попова, В. И. Жуков, *С. О. Стеценко Харковская медицинская академия последипломного образования; *Харковский национальный медицинский университет, г. Харьков Резюме . Исследования мутагенной активности фосфосодержащих органических смесей на бактериях Esherichia Coli штамм trp A 223 и перевиваемой культуре клеток мышиной миеломы Х63 выявили наличие слабых мутагенных качеств исследованных ксенобиотиков. Все соединения в концентрациях 400 і 1000 мг/л обладают бактериостатическим эффектом, а в больших концентрациях в диапазоне от 10 до 80 мг/л они стимулируют мутагенную активность. В зависимости от концентрации, форсфорсодержащие органические соединения способны угнетать синтез белков, РНК и ДНК в культуре клеток Vero. Ключевые слова: ксенобиотики, канцерогенез, мутагенез, атерогенез, угнетение иммунологической недостаточности, репродуктивная функция, бактерии Esherichia Coli, клетки мышиной миеломы Х63.