CDK12 is a member of the cyclin-dependent kinase family that acts as regulator of DNA damage response gene expression. A c.1047-2A>G splice site variant of the CDK12 gene was recently reported to strongly associate with hereditary breast and ovarian cancer in patients of Tatar ethnic origin. To gain more insight into the potential risk and the population spread of the c.1047-2A>G variant, we have genotyped three breast cancer case-control series of Tatar, Bashkir and Kazakh ethnicity. We identified c.1047-2A>G in 6/155 cases and 12/362 controls of Tatar ancestry, 0/96 cases and 9/189 controls of Bashkir ancestry, and 1/131 cases and 0/154 controls of Kazakh ancestry (Mantel-Haenszel odds ratio 0.72, 95% CI 0.30–1.70, p = 0.45). Consistent with the absence of a large effect, bioinformatic analyses predicted that c.1047-2A>G modulates alternative splicing of a NAGNAG sequence rather than constituting a loss-of-function allele, and RT-PCR analyses of c.1047-2A>G heterozygous lymphocytes verified the usage of the predicted alternative acceptor site. Our study confirms a high prevalence of CDK12*c.1047-2A>G in the Tatar and Bashkir population but excludes a role as a clinically actionable high-risk breast cancer mutation.

Nowadays over the world absolute and relative number of aging population dramatically increases with life expectancy up and birth rate down. Aging and senescence assessment are assumed to reflect current changes, internal degeneration and various stressors respond ability (i.e. genetic, environmental and occupational factors) of human organism. Occupational experience time is leading risk factor and indicator for accelerated aging. Last years, many reports concerning aging rate dependence on physical and chemical occupational hazardous factors were published. Summarizing this exposures and their effects on aging reviews are almost absent despite many provided studies. Overview of main occupational neuropsychiatric, physical and chemical risk factors, that causes human aging acceleration presented here. Circadian rhythm disorders, allostatic load, heat stress, local vibration, chemical effects and suspended nanoparticles (fine dust) influences on aging and such signs as Alzheimer’s disease risk increase, telomere length decrease and epigenetic changes and possible interactions between them are also briefly presented. Agricultural, industrial workers, teachers and police officers aging acceleration is detected in results of analysis of biological age markers.

Objective: The development of asthma and its related phenotypes is most likely due to the polymorphism of the so-called modifier genes. The goal of this study was to evaluate the polymorphic locus rs1695 of the GSTP1 gene association with risk factors for developing asthma and its phenotypic manifestations. Methods: This case-control study involved 164 patients with confirmed asthma diagnosis and 147 age- and sex-matched controls. Patients were divided into two groups: with (n = 121) and without complications (n = 43). Among asthmatic patients, 34 manifested hypersensitivity to household allergens. The GSTP1 rs1695 polymorphism was genotyped using the technique of polymerase chain reaction-restriction fragment length polymorphism. Results: There were no differences between patients and controls in allelic or genotype frequencies of polymorphic locus rs1695 of the GSTP1 gene. However, the frequency of the A/A genotype in the patient group with complications was significantly lower than that in complication-free patients (p = 0.040), while the frequency of the G allele was higher in patients with complications (p = 0.030). The frequency of the A/A genotype was decreased in the patient group with an allergic reaction to household allergens in comparison with controls (p = 0.037). Conclusion: These results suggest that the carriage of the A/A genotype of polymorphic locus rs1695 of the GSTP1 gene is a protective factor in the development of complications and an allergic reaction to house allergens among asthmatics, while the carriage of the G allele is associated with an increased risk for asthma complications.

Carbon tetrachloride is a well-studied hepatotropic poison. Animal models of exposure to carbon tetrachloride resemble acute liver damage in humans. This paper presents the study of the...

Introduction. This article presents the results of experimental simulation of the acute toxic effect of cadmium on the rat organism, its distribution in the liver, and kidneys. Activation of the protective mechanism against toxic metal through the metallothionein protein has to reduce the bioavailability of free cadmium. Material and methods. The study was conducted on rats weighing 140-190 g, which was once intragastrically injected with cadmium chloride in an amount of 1/20 LD50. We studied the time intervals: before intoxication, 1, 2, 4, 6, 24, 48, and 96 hours after inoculation. The accumulation of cadmium in the liver and kidneys was measured by atomic absorption spectrometry. The expression of the metallothionein gene (МТ1, МТ2А, МТ3) was determined using RT-PCR on RNA isolated from the same organs. Results. Quantitative differences in the metal content in the liver and kidneys are observed 1 hour after intoxication, with a cadmium content of 250 and 125 times higher than in the control groups, respectively. There is an accumulation of cadmium in the liver with a maximum after 6 hours, and then its redistribution to the kidneys. The pronounced expression of metallothionein with a single acute exposure to cadmium is tissue-specific, so the expression of the MT1 and MT2A genes was greatest in the liver and the MT3 gene in the kidneys. Discussion. After administration cadmium is mainly localized in hepatocytes and its concentration may exceed the ability of metallothionein to bind cadmium ions, which leads to histopathological changes in the liver. In response to the intake of metal in the cell, the expression pattern of many genes, including those associated with the activation of protective reactions, changes. Conclusion. Our data show a single exposure to cadmium to lead to an increase in the content of MT transcript in the liver and kidneys, simultaneously with the accumulation of metal in them. The nature of this accumulation depends on the organ, on the time of exposure, and gene expression also on the form of MT.

Introduction. Cadmium (Cd) is one of the most powerful and dangerous pollutants. Cd exposure is associated with multiple organ damage in both animals and humans. The mechanism of Cd toxicity is the disruption of the body’s antioxidant system (AOS), which leads to transformation of the functional integrity of the liver. The extent of target organ damage can be examined by measuring concentrations of key indicators of hepatocellular injury. The purpose of the work is to evaluate changes in the activity of enzyme markers of hepatotoxicity in the blood serum of laboratory animals after oral exposure to an aqueous solution of cadmium chloride (CdCl2) under the conditions of a subchronic experimental model with a period of remission. Materials and methods. The study was conducted on 40 white outbred rats. Animals of three experimental groups were intragastrically administered a pollutant in various dosages for 3 months. The duration of the remission stage was 1 month. The activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) was determined in the blood serum of animals. Results. When CdCl2 was administered to animals at a dose of 1 μg/kg, an increase in AST activity was observed by 45.9% relative to the control (p=0.006). An increase in the concentration of ALT and LDH is shown. A dose-dependent decrease in the level of alkaline phosphatase was revealed in three groups of animals by 24.7%, 37.5% and 55.4%, respectively (p=0.002). The noted trends indicate pathological processes occurring in hepatocytes. Conclusion. In the course of this study, it was found that under the conditions of a subchronic model of the experiment with a period of remission, cadmium, having a pronounced hepatoxic effect, induces liver damage in experimental animals.