Results of expression studies can be useful to clarify the genotype-phenotype relationship. However, according to data from recent literature, there is a large group of genes that are revealed as differentially expressed (DE) in many studies, regardless of the biological context. Additional analyses could shed more light on the relationships between genes, their differential expression, and diseases. We generated a set of 9972 disease genes from five gene-phenotype databases (OMIM, ORPHANET, DDG2P, DisGeNet and MalaCards) and a report of the International Union of Immunological Societies. To study transcriptomics of disease and non-disease genes in healthy tissues, we obtained data from the Human Protein Atlas (HPA) website. We analyzed the dependency between expression in healthy tissues and gene occurrence in Gene Expression Omnibus series using tools within the Enrichr libraries. The results of expression studies were annotated with Gene Ontology (GO) and Human Phenotype Ontology (HPO) terms. Using transcriptomics analysis of healthy tissues, we validated the previous findings of higher expression levels of disease genes in pathologically linked tissues compared to other tissues. Preferentially DE genes were generally highly expressed in one or multiple tissues and were enriched for disease genes. According to the results of GO enrichment analyses, both down- and up-regulated DE genes most often took part in immune response, translation and tissue-specific processes. A connection between DE-related pathology and the diversity of HPO terms was found. Investigating a link between expression and phenotype contributes to understanding the mode of development and progression of human diseases.

We report that the results of our study indicate that Lactobacillus brevis 47 f strain isolated from the faeces of a healthy individual prevents the manifestations of experimental mucositis induced by treatment of Balb/c mice with the anticancer drug 5-fluorouracil (5 FU; 100 mg/kg i.p. × 3 days). The presence of damage to the intestine and the colon was determined by a morphometric analysis of specimens including the height of villi, the amount of goblet cells and infiltrating mononuclear cells, and the expression of the proliferative Ki-67 antigen. Changes in the lipid peroxidation in the blood and the intestine were determined by severalfold increase of the concentration of malonic dialdehyde. Oral administration of L. brevis 47 f strain prior to 5 FU decreased the drug-induced morphological and biochemical changes to their respective physiological levels; the ability of intestinal epitheliocytes to express Ki-67 was partially restored. These effects of L. brevis 47 f strain were more pronounced or similar to those of the reference compound Rebamipid, a quinoline derivative known to protect the gut from drug-induced toxicity. Thus, the new lactobacilli strain attenuates the severity of 5 FU-induced enteropathy.

To study the ability of metal salts and pharmacologically active drugs to induce the oxidative stress and SOS response in bacteria, a set of lux-biosensors was used. The sensors were based on three E. coli strains carrying recombinant plasmids with lux-operon fused to the promoters of SoxS (superoxide dismutase), KatG (catalase-peroxidase) and ColD (colicin D) genes. The created biosensors were used to analyze the activity of 47 substances, with 16 of them identified to induce SOS-response and 6 - to induce oxidative stress. The results observed were compared to the previously published data on the mutagenic activity of the same 47 substances evaluated using Ames test. The comparison had shown full coincidence for 42 from 47 substances analyzed. We discuss the possibility to use the lux-based biosensors for the screening of the genetic activity of chemical compounds.

The aim of this study was to assess the applicability of the bacterial lux biosensors for genotoxicological studies. Biosensors are the strains of E. coli MG1655 carrying a recombinant plasmid with the lux operon of the luminescent bacterium P. luminescens fused with the promoters of inducible genes: recA, colD, alkA, soxS, and katG. The genotoxicity of forty-seven chemical compounds was tested on a set of three biosensors pSoxS-lux, pKatG-lux and pColD-lux, which allowed us to estimate the oxidative and DNA-damaging activity of the analyzed drugs. The comparison of the results with the data on the mutagenic activity of these drugs from the Ames test showed a complete coincidence of the results for the 42 substances. First, using lux biosensors, we have described the enhancing effect of the heavy non-radioactive isotope of hydrogen deuterium (D₂O) on the genotoxicity of chemical compounds as possible mechanisms of this effect. The study of the modifying effect of 29 antioxidants and radioprotectors on the genotoxic effects of chemical agents showed the applicability of a pair of biosensors pSoxS-lux and pKatG-lux for the primary assessment of the potential antioxidant and radioprotective activity of chemical compounds. Thus, the results obtained showed that lux biosensors can be successfully used to identify potential genotoxicants, radioprotectors, antioxidants, and comutagens among chemical compounds, as well as to study the probable mechanism of genotoxic action of test substance.

Background. Natural aquatic ecosystems are the habitat of many organisms, a source of drinking water, a resource for human activities and are subjected to anthropogenic pressure. In this regard, interest in studying the genotoxicity and mutagenicity of surface waters has increased significantly. The aim of this study is to investigate the cytotoxic, genotoxic and mutagenic effects of the surface waters of the suburban area of Almaty. Material and methods. The research materials were water samples of the rivers Esik, Turgen and Lake Esik. The atomic absorption method, lux-test, cytogenetic tests (Hordeum vulgare L.), phytotoxicity test (Allium cepa L.) and embryotoxicity (Danio rerio H.) were used. Results. Physico-chemical water analysis revealed an excess of MPC for Mn, Pb, Cd, Zn. Using the lux-test on E. coli KatG strains, the pro-oxidant activity of Esik R. water. On the plant test objects revealed toxicity and mutagenicity of water samples. The results of bio-testing of natural waters with D. rerio revealed their high toxicity and teratogenicity for embryos at all stages of development. Conclusion. The results of this study obtained on various test-systems and test-objects indicate that surface waters are contaminated by environmentally dangerous factors that pose a threat to biota and human health.

The review highlights the history of genetic toxicology as a distinct research area, as well as the issues of genetic toxicology and development of its methodology. The strategies and testing...