The Role of Immunomodulator Betaleukin in Recovery of Hepatocytic Ploidy Profile in Delayed Terms after Irradiation.

We studied the radioprotective effect of betaleukin administered to (CBA×C57Bl/6)F1 mice in single doses of 50 and 3 µg/kg 2 and 22 h, respectively, prior to long-term (21 h) whole-body low-intensity (10 mGy/min) γ-radiation (137Сs; total dose 12.65 Gy). Hepatocyte ploidy, a biomarker of metabolic disorders of the liver, was evaluated, and nuclearity and ploidy indices were calculated. In 10 months after irradiation, a significant decrease in the ploidy index was revealed in the group of irradiated mice, while in animal receiving 3 or 50 µg/kg betaleukin, this parameter did not differ and even surpassed the control level, respectively. Thus, in vivo assessment of hepatocytic ploidy profile in mice revealed negative delayed effects of γ-irradiation in a dose of 12.65 Gy and a protective effect a single injection of immunomodulator betaleukin.

Behavioral Responses and Immune and Cytogenetic Parameters of Food-Restricted Mice.

The experiments on mice showed that subchronic food restriction to 40 and 8% of unrestricted ration is a strong stressor inducing devastation of lymphoid organs, primarily the thymus and spleen. The mice in the group with severe food restriction (8% of normal ration) demonstrated increased front paw grip force. We also observed an increase in spontaneous motor activity in these animals correlated with food restriction. Food deprivation led to inhibition of proliferative activity of the bone marrow cells and suppression of erythropoiesis. Moreover, severe food restriction was accompanied by a decrease in the number of double-strand DNA breaks evaluated by the release of γH2AX+-cells and the ratio of polychromatophilic erythrocytes.

The Dependence of the Mutagenic Effect on the Dose of X-Ray Irradiation in an In Vivo Experiment on Female (CBA×C57Bl/6)F1 Mice.

We studied the mutagenic effect of X-ray irradiation in doses of 0.5, 1, and 1.5 Gy on female (CBA×C57Bl/6)F1 mice. The mutagenic effect (assessed by the parameter "frequency of bone marrow polychromatophilic erythrocytes with micronuclei") linearly depended on the dose of X-ray irradiation in the range of up to 1 Gy and reached the plateau at 1.5 Gy. The fraction of polychromatophilic erythrocytes was 45, 45, and 46% under control conditions (without exposure) and exposure to the irradiation in the doses of 0.5 and 1 Gy, respectively. Irradiation in a dose of 1.5 Gy induced a slight inhibition of erythropoiesis. These data confirm the hypothesis on possible death of highly aberrant erythrocyte precursors after irradiation in high doses.

Structural and Functional Analysis of the Small Intestine in Rats After Six-Month-Long Exposure to Multiwalled Carbon Nanotubes.

Structural and functional analysis of the small intestinal villi in outbred rats was performed after treatment with multiwalled carbon nanotube suspension in comparison with the effects of fine charcoal suspension. Chronic (6 months) exposure to nanotubes in a concentration of 0.2 mg/liter and, particularly, 0.5 mg/liter induced significant changes in the small intestine manifested in a decrease in the number of villi without changes in the brush border integrity, increase in the number of destructed villi, and appearance of villi with apical necrosis. These abnormalities were not observed after treatment for a shorter period of time (2 months).

[Cytogenetic status of children in the hygienic assessment of the air pollution by odorous substances].

For the first time the impact of odorous emissions from the enterprise for the production of chewing gum on the cytogenetic status of children, residing in the distance of 0,9 and 6 km, was studied. Specific weak mint and fruity odour in the air in the placement of the enterprise may be related to the presence of menthol, menthone, pinene, limonene, ethyl acetate and other compounds containing in the emissions. There were no differences in cytogenetic status of children in both groups (by frequency of micronuclei, protrusions, binucleated cells, apoptosis).

[Morphological comparative assessment of in vivo 2-week oral exposure of silver nanoparticles and silver sulfate on the mice liver].

Currently the problem of the impact of nanoparticles and nanomaterials on human health remains to be poorly understood. As in our studies of the impact of silver nanoparticles on rats liver as well in works of other researchers there were investigated morphofunctional indices under peroral exposure. Although all researchers took different sizes, doses and concentrations of silver nanoparticles, various exposure time and different stabilizers, the same effects had been obtained, which, however, were occurred under both different doses and time of exposure. However, it was interesting to compare the impact of silver nanoparticles with reference substance - silver sulfate on the mice liver with the previously evaluated effect produced on the rats ' liver. By ourselves there was executed the morphological comparative evaluation of in vivo oral 2-weeks exposure of 4 concentrations (0.1; 5; 50 and 500 mg/l) of silver nanoparticles with size of 14 nm, stable arabian gum 1:7 by weight, and of 4 similar concentrations of silver sulfate on the liver of male mice СВАхС57В1/6 weighing 25-35g. 2 groups were considered as control: intact mice and mice received gum in water. Results of the exposure were assessed according to 10 morphological and functional indices. The impact of nanosilver was shown to initiate from its concentration of 50 mg/l and to express in the gain of the index of alteration of the cytoplasm of hepatocytes with the increasing in both severity of steatosis and the number of micronecroses, persisting at the same level at concentrations of 500 mg/l and with the elevation of the index of alteration of nuclei of hepatocytes, while the similar effect develops under the influence of silver sulfate at a concentration of 500 mg/l only. The remaining investigated morphofunctional indices did not differ significantly in all groups of mice. Unlike previously executed studies on rats, mice appeared to be sensitive to the effects of nano-silver more than to silver sulfate.

[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.

Studies of antimutagenic effects of vitamins A and C in humans.

We studied antimutagenic effects of vitamins A and C (in recommended daily doses for 30 days) and their effects on the kinetics of human buccal epitheliocytes. Buccal swab specimens were collected in 29 students before and after vitamin course. The cytogenetic parameters (cells with micronuclei and protrusions) and parameters of proliferation (binuclear cells and cells with double nuclei) and nucleus destruction (karyopyknosis, karyorrhexis, karyolysis, etc.) were analyzed. The levels of cells with micronuclei and total level of cytogenetic disorders decreased by 38% after vitamin course, which confirmed their antimutagenic effect. A slight increase in the percentage of apoptotic cells seemed to reflect more active process of elimination of genetically damaged cells.

[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.

[Effect of multi-walled carbon nanotubes on the morphofunctional state of the small intestine cells of mice].

The experiment was conducted in male mice SBAchS57Vl/6 and Balb/c, which consumed water, obtained from the use of carbon nanotubes. in a free drinking regimen for 2 weeks (mice SBAchS57Vl/6) and 2 months (mice Balb/c) Control group consisted of three groups of animals: intact and mice received fine coal in the same concentrations as under the impact of the nanotubes. Under exposure to the maximal of the studied concentration of carbon nanotubes a significant change in the fine structure of the villi of the small intestine was found in the form of increasing the number of unstructured villi and proliferation of epithelial cells, most pronounced in duration of exposure until 2 months.

[Cytogenetic monitoring for assessment of human environmental safety].

Cytogenetic monitoring allows to identify groups and individuals with elevated levels of genomic instability, to determine the presence of genotoxic factors in the inspected area to justify the conduct of hygienic measures. An algorithm for cytogenetic monitoring with the usy of multi-organ karyological test, baseline of indices of cytogenetic effect, cell proliferation and apoptosis are presented, the index of accumulation of cytogenetic damage as a the basis for assessment of the three level of risk of cytogenetic abnormalities, is proposed.

[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.

[Necessity to evaluate the genetic safety of xenobiotics in mammalian experiments].

The need to obligatorily evaluate the genetic safety of factors in in vivo experiments is substantiated by the body's protective systems, toxicokinetic features, organ specificity, and the pattern of time and dose dependencies. To substantiate the need for in vivo studies, the author gives the results of long-term studies by the laboratory of genetic monitoring and considers the features of mutagen testing in mammalian versus in vitro experiments. She presents the system developed at the Institute to evaluate the mutagenic properties of environmental factors, by taking into account the organ specificity, the basis of which is a multiorgan karyological analysis. Being a good tool to study the regularities of the toxic action of xenobiotics, this approach is of important scientific and practical value.

[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.

[Complex study of the mutagenic effect of soil pollutions with petrochemical products in the Chechen Republic].

A study to evaluate congenital morphogenetic variants (CMGVs) and the association of the polymorphism of the xenobiotic detoxification and repair genes with cytogenetic parameters was conducted for the first time in children living in different climatic zones and areas polluted with primary petroleum refining products. Analysis of CMGVs and cytogenetic parameters in children points to the total genotoxic impact of oil pollutions. The children's higher sensitivity to environmental pollution is associated with the polymorphism of the detoxification gene, with the base excision repair gene XRCC1 in particular.

[Values of the micronucleus test on animal epithelial cells exposed to titanium dioxide].

The genetic safety of titanium dioxide (TD)-containing foods and cosmetic products has been little investigated. The study evaluated the mutagenic activity of TD in the micronucleus test with animal visceral mucosal epithelial cells. Two simethicone-coated anatase samples (mean size 160 and 33.2 nm) were inserted into the mouse stomach in doses of 40-200-1000 mg/kg seven times and applied as an ingredient of 10 and 25% cream (doses 250 and 625 mg/kg, respectively) to the hair-sheared rat skin once for 4 hours. Analysis of cytogenetic disorders (micronuclei, protrusions, and the atypical form of the nucleus) revealed no mutagenic properties of TD on the mucosal epithelium of the mouse and rat intestine, mouse prostomach, and rat uterine bladder. Enhanced mitotic activity was observed in all the study tissues after exposure of both samples to TD given in some or in all (in the rat urinary bladder mucosal epithelium) doses.

Mutagenic activity of acrylamide in the rat thyroid cells under conditions of a subacute experiment.

Experimental mutagenic effect of acrylamide on thyroid gland cells was studied by an extended micronucleus test. Acrylamide in doses corresponding to 0.004-0.1 LD(50) increased the incidence of thyroid follicular cells (A-cells) with micronuclei and other karyological parameters in exposed rats after hemithyroidectomy. This cytogenetic effect allows regarding acrylamide as a mutagen for the thyroid gland and as a carcinogen for this organ.