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.
Purpose
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.
Methods
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).
Results
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.
Conclusions
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.
The article is devoted to the urgent problem of formation of reading literacy of modern schoolchildren, which is interpreted as the most important type of functional literacy, based on the ability to ...operate various types of texts, understanding their deep meaning and correct interpretation. The authors reveal the specifics of the formation of reading literacy in Russian language classes, using regionally colored texts as a meaning-forming content component. The materials of the article reflect the data of the pedagogical experiment, which allows to adjust the methodological strategies of the teacher in a significant way. The authors state that despite the need to comply with the normative requirements set forth in the updated FSES, modern teachers do not work on the formation of functional literacy in the system. A comprehensive analysis of the educational results of the educational process allowed the authors of the article to argue that the content basis of lessons aimed at the formation of functional literacy can be regionally colored texts that allow building lines of in-depth dialogue against the background of understanding the meanings of the culture of the small homeland.
After 48-72 hours, loss of α-tocopherol, increase of susceptibility to oxidation, and accumulation of lipid peroxidation products in LDL are observed. ...multiple modification of LDL is a cascade of ...sequential changes in lipoprotein particle, namely: desialylation, loss of lipids, size reduction, increase of electronegative charge, lipid peroxidation in LDL.
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•One-step and diastereoselective approach for benzofisoindole-4-carboxylic acids.•Previously unknown tandem N-acylation/IMDAV/Alder-ene reaction was discovered.•Benzofisoindoles ...display antiviral activity against the influenza virus H1N1.
The reaction between readily accessible N-aryl-3-phenylallylamines and maleic anhydride led to unexpected products – polysubstituted hydrogenated benzofisoindole-4-carboxylic acids. This transformation proceeds through a previously unknown sequence of steps: N-acylation of the allylamine with maleic anhydride, intramolecular Diels-Alder reaction of the vinylarene in the intermediate N-maleamide, and Alder-ene reaction of the products of the previous two steps. Selected benzofisoindoles displayed antiviral activity.
The present review article considers some chronic diseases of vascular and metabolic genesis, the causes of which may be mitochondrial dysfunction. Very often, in the long course of the disease, ...complications may occur, leading to myocardial infarction or ischemic stroke and, as a result, death. In particular, a large percentage of human deaths nowadays belongs to cardiovascular diseases, such as coronary heart disease (CHD), arterial hypertension, cardiomyopathies, and type 2 diabetes mellitus.
The aim of the present review was the analysis of literature sources, devoted to an investigation of a link of mitochondrial DNA mutations with chronic diseases of vascular and metabolic genesis.
The analysis of literature indicates the association of the mitochondrial genome mutations with coronary heart disease, type 2 diabetes mellitus, hypertension, and various types of cardiomyopathies.
The detected mutations can be used to analyze the predisposition to chronic diseases of vascular and metabolic genesis. They can also be used to create molecular-cell models necessary to evaluate the effectiveness of drugs developed for the treatment of these pathologies. MtDNA mutations associated with the absence of diseases of vascular and metabolic genesis could be potential candidates for gene therapy of the said diseases.
There are several types of mitochondrial cytopathies, which cause a set of disorders, arise as a result of mitochondria's failure. Mitochondria's functional disruption leads to development of ...physical, growing and cognitive disabilities and includes multiple organ pathologies, essentially disturbing the nervous and muscular systems. The origins of mitochondrial cytopathies are mutations in genes of nuclear DNA encoding mitochondrial proteins or in mitochondrial DNA. Nowadays, numerous mtDNA mutations significant to the appearance and progress of pathologies in humans are detected. In this mini-review, we accent on the mitochondrial cytopathies related to mutations of mtDNA. As well known, there are definite set of symptoms of mitochondrial cytopathies distinguishing or similar for different syndromes. The present article contains data about mutations linked with cytopathies that facilitate diagnosis of different syndromes by using genetic analysis methods. In addition, for every individual, more effective therapeutic approach could be developed after wide-range mutant background analysis of mitochondrial genome.
In this review article, we analyzed the literature on the creation of cultures containing mutations associated with cardiovascular diseases (CVD) using transfection, transduction and editing of the ...human genome.
We described different methods of transfection, transduction and editing of the human genome, used in the literature.
We reviewed the researches in which the creation of сell cultures containing mutations was described. According to the literature, system CRISPR/Cas9 proved to be the most preferred method for editing the genome. We found rather promising and interesting a practically undeveloped direction of mitochondria transfection using a gene gun. Such a gun can direct a genetically-engineered construct containing human DNA mutations to the mitochondria using heavy metal particles. However, in human molecular genetics, the transfection method using a gene gun is unfairly forgotten and is almost never used. Ethical problems arising from editing the human genome were also discussed in our review. We came to a conclusion that it is impossible to stop scientific and technical progress. It is important that the editing of the genome takes place under the strict control of society and does not bear dangerous consequences for humanity. To achieve this, the constant interaction of science with society, culture and business is necessary.
The most promising methods for the creation of cell cultures containing mutations linked with cardiovascular diseases, were system CRISPR/Cas9 and the gene gun.
Although the effect of pollution on forest health and decline received much attention in the 1980s, it has not been considered to explain the ‘Divergence Problem’ in dendroclimatology; a decoupling ...of tree growth from rising air temperatures since the 1970s. Here we use physical and biogeochemical measurements of hundreds of living and dead conifers to reconstruct the impact of heavy industrialisation around Norilsk in northern Siberia. Moreover, we develop a forward model with surface irradiance forcing to quantify long‐distance effects of anthropogenic emissions on the functioning and productivity of Siberia’s taiga. Downwind from the world’s most polluted Arctic region, tree mortality rates of up to 100% have destroyed 24,000 km2 boreal forest since the 1960s, coincident with dramatic increases in atmospheric sulphur, copper, and nickel concentrations. In addition to regional ecosystem devastation, we demonstrate how ‘Arctic Dimming’ can explain the circumpolar ‘Divergence Problem’, and discuss implications on the terrestrial carbon cycle.
In this study, we present the combined evidence from dendroecology, biogeochemistry and process‐based forward modelling to address the direct and indirect effects of industrial pollution on the functioning and productivity of boreal forest ecosystems. In addition to the quantification of the exceptional rate of environmental devastation around Norilsk, the world’s most polluted Arctic region, we demonstrate that anthropogenic‐induced ‘Arctic Dimming’ can explain the yet unresolved ‘Divergence Problem’ in tree‐ring research.
Chronic stress is a combination of nonspecific adaptive reactions of the body to the influence of various adverse stress factors which disrupt its homeostasis, and it is also a corresponding state of ...the organism's nervous system (or the body in general). We hypothesized that chronic stress may be one of the causes occurence of several molecular and cellular types of stress. We analyzed literary sources and considered most of these types of stress in our review article. We examined genes and mutations of nuclear and mitochondrial genomes and also molecular variants which lead to various types of stress. The end result of chronic stress can be metabolic disturbance in humans and animals, leading to accumulation of reactive oxygen species (ROS), oxidative stress, energy deficiency in cells (due to a decrease in ATP synthesis) and mitochondrial dysfunction. These changes can last for the lifetime and lead to severe pathologies, including neurodegenerative diseases and atherosclerosis. The analysis of literature allowed us to conclude that under the influence of chronic stress, metabolism in the human body can be disrupted, mutations of the mitochondrial and nuclear genome and dysfunction of cells and their compartments can occur. As a result of these processes, oxidative, genotoxic, and cellular stress can occur. Therefore, chronic stress can be one of the causes forthe occurrence and development of neurodegenerative diseases and atherosclerosis. In particular, chronic stress can play a large role in the occurrence and development of oxidative, genotoxic, and cellular types of stress.
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