A study of the genotoxic activity of fungicide carbendazim was carried out. It was demonstrated that the tested technical grade active ingredient of carbendazim in the dose range of 125-2000 mg/kg body weight induced a statistically significant dose-dependent increase in the frequency of micronucleated polychromatic (PCE) and normochromatic erythrocytes (NCE) in the bone marrow of CD-1 mice. After administration of carbendazim at doses of 250-2000 mg/kg body weight, the accumulation of cells containing two or more micronuclei was observed. According to the results of comet assay, there was no increase in the level of breaks and alkali-labile sites in the DNA of the mouse bone marrow and liver cells after administration of technical grade carbendazim at doses up to 2000 mg/kg body weight. It is therefore suggested that the observed accumulation of cells with micronuclei is due to the aneugenic effect of carbendazim. In addition, a dose-dependent increase in the proportion of macrocytes/gigantocytes and dumbbell-shaped cells with constrictions among PCEs and NCEs was observed, which might be indicative of the inhibitory effect of the test pesticide on cytokinesis. The accumulation of polychromatophiles with pyknotic nuclei after exposure to carbendazim is probably caused by the distortion of nuclear extrusion. A possible general mechanism underlying the impairment of karyokinesis, cytokinesis, and nuclear extrusion in mammalian bone marrow erythroid cells is discussed.
In order to overcome resistance to individual pesticides and improve their effectiveness, formulations containing two or more active substances are constantly being developed and put on the market over recent years. Mixtures of residual amounts of pesticides can be present in water and food and enter the human and animal bodies. However, the combined effect of pesticides on living organisms, including genetic structures in cells, has not been studied enough and it is not yet possible to predict the genotoxic effects of their mixtures based on available data. The purpose of this review was to collect and summarize literature information on the genotoxicity of pesticide combinations obtained at different objects. The results of studies conducted in different countries of the world are discussed, examples of detected synergistic, additive and antagonistic effects are given, indicating the need for testing the genotoxicity of preparative forms of pesticides containing several active substances, as well as mixtures of jointly used pesticides in order to ensure the safe use of pesticides for public health.
Introducton. Due to the increasing volumes of toxic substances entering the environment, including genotoxicants, it becomes necessary to conduct studies to assess their impact on people living in areas with high levels of pollutants, as well as people working in hazardous conditions. Epidemiological studies, in which damage to hereditary structures in human cells is assessed, in peripheral blood lymphocytes and buccal epithelial cells mainly, are carried out to determine the real genetic risk. Materials and methods. Samples of buccal epithelium were used. The study involved 69 people: 28 in the control group and 41 in the group of persons who were in contact with pesticides. The cytomorphological analysis took into account the following indicators: cytogenetic, cell proliferation, early and late destruction of nuclei. Results. The frequency of occurrence of the cells with micronuclei and protrusions in persons who were in contact with pesticides during their professional activities was increased 2.2 times, the frequency of cells with atypical nuclei - 2.5 times (differences in cytogenetic parameters between the groups were statistically insignificant). Statistically significant changes in the proliferation indicator were revealed - the frequency of cells with two nuclei (1.6 times), as well as the destruction indicators - karyorrhexis (4.5 times more often in nonsmokers and 8.2 times more often in smokers who work with pesticides) and karyolysis (the frequency of cells with initial karyolysis was increased by 3.4 times and 3.2 times with complete karyolysis). The index of accumulation of damage disorders was shown to be 4 times higher. Conclusion. The obtained data indicate an increased risk of damage to the genetic apparatus of cells in persons whose professional activities are associated with testing and using pesticides.
The article discusses the directions of research in the field of genetic toxicology, which allow solving problems important for hygiene, aimed at ensuring the genetic health of the population. The main areas of research are: assessment of the genetic hazard of environmental factors and the level of pollution by genotoxicants; analysis of the total mutagenic activity of mixtures of chemical pollutants; control over mutational events in the somatic cells of people working in hazardous production conditions, which is necessary to improve the prevention, diagnosis and treatment of occupational diseases and multifactorial pathology; study of individual genetically determined human sensitivity to the impacts of adverse environmental factors in order to improve professional selection and development of personalized preventive medicine; assessment of mutagenicity in short-term tests to predict the carcinogenicity of the studied substances; search for antimutagens. The methods used in genetic toxicology are described. The main directions and results of the work of the Department of Genetic Toxicology of the FBES “Federal Scientific Center of Hygiene named after F.F. Erisman” of the Rospotrebnadzor are given. Conclusion. The results of genotoxicological studies allow us to evaluate and establish hazard classes of the tested substances, predict possible long-term effects. Monitoring of mutational events in the somatic cells of people exposed to various environmental factors, assessment of individual human sensitivity to specific factors or their combinations make it possible to identify and evaluate potentially dangerous factors for genetic health, develop preventive measures and carry out reasonable professional selection of persons to work in harmful production conditions.
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