[GENETIC EVALUATION OF CONTROL VARIANTS OF STRAINS SALMONELLA TYPHIMURIUM, USED IN THE TEST SALMONELLA/MICROSOME (Ames test)].

There were analyzed data of controls with solvents (DMSO and distilled water) of experiments performed in the laboratory of genetic monitoring in 2004-2014 on Salmonella typhimurium TA 100, TA 98 and TA 97 strains in the versions without and in the presence of metabolic activation. For all strains there was no revealed effect of the either solvent or system of metabolic activation on the average number of colonies of revertants in control. Generalized parameters (historical control) of the average number of colonies of revertants per plate: TA 100--number of experi- ments--317, average--118; 95% intervals of 71-165; TA 98--number of experiments--389, mean--22; 95% intervals 9-36; TA 97--the number of experiments--217, average--142; 95% intervals of 94-191.

[Cytogenetic status of patients with cancer of the gastrointestinal tract before and after treatment].

Aim of this study was to analyze the karyological indicators in exfoliated cells in patients with cancer of the gastrointestinal tract. There was revealed statistically significant (p < 0.01) increase of all parameters in buccal and nasal epithelium in such kind of patients compared to healthy persons. These changes were systemic in nature and reflected the general state of the organism.

[Study of cytogenetic and cytotoxic effect of non-contact electrochemically-activated waters in the five organs of rats].

For the first time the multiorgan karyological analysis of five organs of rats was applied for the study of the cytogenetic and cytotoxic action of the four types of non-contact electrochemically activated water in the 30-days in vivo experiment. The effects of investigated waters were not detected in bone marrow polychromatic erythrocytes. "Anolyte" (ORP = -362 mV) did not have a negative effect on rats. "Catholyte-5" (ORP = +22 mV) and "Catholyte-25" (ORP = -60 mV) induced cytogenetic abnormalities in the bladder and fore stomach. The same catholytes and "Catholyte-40" (ORP = -10 mV) changed the proliferation indices: increased the mitotic index in the fore stomach epithelium and reduced the frequency of binucleated cells in the fore stomach, bladder and lungs. The increase in the rate of cells with cytogenetic abnormalities on the background of the promotion of mitotic activity can be considered as a manifestation of the negative effect, typical for catolytes, but the effect of each out of them has its own features.

[Actual problems of genetic toxicology].

The review deals with current issues of genetic toxicology and aims to develop this science at the contemporary stage. We study general approaches to assessing the genotoxic and mutagenic activity of environmental factors; to constructing a regulatory system of chemical compounds that considers the mutagenic effect in Russia and abroad; and to determining modem methods for assessing the organ specificity of mutagens, alternative methods of genetic toxicology, the mutagenic action of various factors in the survey of population, and the abilities of toxicogenomics to identify the mutagenic properties of the environment.

[Harmonization with international approaches to guidance documents on methods of assessment of the mutagenic properties of chemical environmental factors].

Evaluation of mutagenic activity--an indispensable element of the toxicological characteristics of chemicals in their hygienic regulation. In the article there is performed an analysis of the adopted in the Organization for Economic Cooperation and Development (OECD) and in Russia guidance documents on methods of assessment of the mutagenic properties of chemicals. In the OECD there are 17 manuals, each of which describes a single method, in Russia there were approved five guidance documents for specific groups of chemicals (drugs, pesticides, nanomaterials, substances normalized in the water and the air), which represent the basic and auxiliary methods of testing mutagens. Basic methods aimed to the evaluation of gene, chromosomal and genomic mutations include: assessment of gene mutations in bacteria, methods for estimating mutations in cell cultures of human and mammals in vitro, methods for inspecting mutations in somatic and germ cells of mammals in vivo. Analysis of Russian documents shows that the protocols of basic tests of assessment of the mutagenic activity are close to the protocols of the OECD. It is necessary to publish guidance documents on tests of assessment of the mutagenic activity of chemicals harmonized with the OECD documents.

[Estimation of genetic safety of nanomaterials].

Problems pertaining to the estimation of genetic safety of nanomaterials are considered. Comparative analysis of current approaches to testing mutagenicity in this country and abroad is presented. The necessity of mandatory evaluation of genotoxic and mutagenic properties of modern nanomaterials in accordance with international standards is substantiated. The system of the existing methods for the purpose should be supplemented by new scientifically sound and verified techniques. Methodological peculiarities of the assessment of organ-specific nanomaterials are described. It is recommended to correct certain provisions of the approved Guidelines 1.2.2520-09 concerning mutagenic properties of nanomaterials.

[Relationship of structural-functional (histological and cytological) parameters with cytogenetic and cytotoxic ones in the evaluation of the influence of environmental factors on the organism].

The paper gives an assessment of the association of structural-functional (histological and cytological), cytogenetic, and cytotoxic changes in the analysis of various exposures of the body during both experiments (oral acrylamide) and population examinations (impact of pulp-and-paper mill waste on the nasal and oral mucosae). The assessment of the association of the study parameters is shown to serve to more completely objectify the pattern of actuating factors.

[Karyological and immunological parameters in children under conditions of varying ambient air pollution].

The cytological status, proliferation, and apoptosis of the buccal epithelium and the level of secretory immunoglobulin A were studied in 90 children living in a large ferrous metallurgy center (Tula). There were increases in the degree of cytogenetic impairments, a change in cell kinetic processes, and a reduction in local immunity in children in a more polluted area. There was a high significant correlation of karyological and immunological parameters with some chemical ambient air pollutants.

[The cytogenetic status of children living in the vicinity of a pulp-and-paper mill].

To evaluate the cytogenetic and cytotoxic effects of a set of pollutions in the town of Koryazhma, the investigators made a complete karyological analysis (cytogenetic, apoptotic, and indirect proliferation parameters) of buccal and nasal epithelial exfoliative cells in two groups of old school age children living at various distances from a pulp-and-paper mill (PPM). The residential area that is adjacent to the PPM can be considered to be poor in the influence of genotoxic factors since there were 1.6- and 1.65-fold increases in cytogenetic disorders and cells with an atypically shaped nucleus, respectively, with a 1.57-fold reduction in the level of cell apoptosis. Karyological changes were revealed in the nasal mucosa, rather than in the buccal mucosa, which permitted one to recommend for the evaluation of the influence of environmental factors, the impact of ambient air pollution in particular, and to conduct cytogenetic studies on the cells of not only the buccal epithelium (that has been better studied), but also those of the nasal epithelium.

[Impact of ambient air pollution by a pulp-and-paper mill on the cytological status of the nasal and oral mucosa in children].

The cytological state of nasal and oral mucosae in the children and adolescents living in the town of Koryazhma was evaluated at the schools located differently from the Kotlas pulp-and-paper mill (PPM). All the Kozyazhma children under examination were found to have an increased epithelocytic alteration index, which is likely to suggest cytotoxic exposure, which was shown to a greater extent with the duration of residence at the school more adjacent to the PPM. The first-form pupils from the school locates more closely to the PPM were found to showed a higher index of natural microflora colonization with buccal epitheliocytes and a trend for an increase in the epitheliocytic differentiation coefficient characterizing the high incidence of diseases.

[Analysis of the mutagenic activity of aqueous and buffer extracts from oil-polluted soil samples].

The Ames test on Salmonella typhimurium TA 100 and TA 98 strains were used to study the mutagenic activity of aqueous (pH 7.4) and buffer (pH 4.5) extracts from soil samples containing different oil levels (from 16 to 3526 mg per kg soil), which had been taken from different areas of a town, and buffer extracts from model soil samples added by crude West-Siberian oil (160-15625 mg/kg). The extracts from all soil samples showed no mutagenic activity. The buffer soil sample extract containing oil in the amount of 12290 mg/kg and oil and coal combustion products had a mutagenic effect with metabolic activation on the TA 98 strain. It is suggested that the mutagenic effect of this sample is associated with oil and coal combustion products.

[Approaches to assessing the human risk of mutagens].

The assessment of the human risk of mutagens is a constituent of the general assessment of the risk of environment-pollutant chemicals to the population's health. An algorithm of assessing the risk of mutagens is proposed. Stage 1 (hazard identification) is to provide an expert analytical characterization of the mutagenic potential of the chemicals polluting the study object. Stage 2 (hazard characterization) is to analyze the quantitative dependences of the effect of mutagens in gametes and somatic cells of man and mammals. Stage 3 (effect evaluation) is to characterize the sources of pollution and the doses of mutagens affecting the population. Stage 4 (risk characterization) is to calculate the risk of mutagens to the population and individuals.

Evaluation of mutagenic activity of dioxazid by the polyorgan micronuclear method in experiments on rats.

The mutagenic effect of antituberculous drug dioxazid was studied on rats receiving this preparation in a dose of 25 mg/kg (in conversion to dioxidine) via inhalation route for 3 months. The percentage of cells with micronuclei and the content of polychromatophilic erythrocytes among all bone marrow erythrocytes and percentage of cells with micronuclei, protrusions, and binucleated cells in the lungs and urinary bladder were evaluated. Dioxazid caused no changes in organs, except the increase in the percentage of binucleated cells in bladder epithelium, which attests to minor cytotoxic effect of the drug for this organ.

[Role of genetic studies in the evaluation of the human influence of environmental factors].

The authors propose to include not only a control of human populations, but also environmental factors (chemical, physical, and biological), and objects (to estimate the cumulative mutagenic activity of water, air, soil, and foodstuffs) in order to ensure human genetic safety. For evaluation of human cell genetic damage, they also propose to use the noninvasive multiple organ micronuclear test, by taking into account additional cardiological parameters. The results of this monitoring makes it possible to define higher genetic risk areas for warranting the necessity, priority, and nature of prophylactic measures and to identify a risk group of individuals to be thoroughly examined and to undergo health-promoting measures.

Study of mutagenic activity of dioxidine by the polyorgan micronuclear method.

Antibacterial preparation dioxidine administered four times in doses of 10, 100, and 300 mg/kg increased the incidence of micronucleated cells in the bone marrow, lungs, and large intestine of mice. Bone marrow cells were most sensitive, while cells of the lungs and large intestine exhibited lower sensitivity to the cytogenetic effect of dioxidine.

[Genetic approaches to evaluating safety of human environmental factors]. / Geneticheskie podkhody k otsenke bezopasnosti factorov sredy obitaniia cheloveka.

Main achievements made in genetic toxicology in the past 40 years are analyzed. Guidelines for estimating gene toxic agents have been developed and a database pertaining to the mutagenicity of several thousands of chemicals has been set up. Experience in evaluating human mutagenic effects has been accumulated. It is necessary to develop a current toxicological and sanitary classification of mutagenic xenobiotics, to take a stock of environmental gene toxic agents by their activity and pollution in the areas of Russia, to work out criteria for the actual genetic hazards (a genetic risk) of mutagens entered the human habitat, to study a human individual response to mutagenes and to make "a genetic certification", and to analyze the feasibility of human genome protection from environmental mutagenic factors.