Cytogenetic Effects of Carbendazim on Mouse Bone Marrow Cells

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Cytogenetic Effects of Carbendazim on Mouse Bone Marrow Cells N. A. Ilyushina* Erisman Federal Scientific Center of Hygiene, Mytishchi, Moscow oblast, 141014 Russia *e-mail: [email protected] Received October 22, 2019; revised December 6, 2019; accepted January 14, 2020

Abstract—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. Keywords: carbendazim, micronuclei, aneugenic effect, erythropoiesis, bone marrow, cytokinesis, nuclear extrusion, comet assay DOI: 10.1134/S1022795420090094

INTRODUCTION Pesticides from the fungicide group are compounds designed to control fungal diseases of plants. Currently, both chemical and biological fungicidal agents are used. Compounds of different classes are used as chemical fungicides, including strobilurins, benzimidazoles, morpholines, quinones, imidazoles, triazoles, etc. Carbendazim belongs to the class of benzimidazoles and is a metabolite of benomyl and thiophanatemethyl. Carbendazim-based formulations have been and are still being used in a number of countries as systemic fungicides against diseases of wheat, barley, rye, sugar beets, sunflowers, apple trees, citrus fruits, seed potatoes, and other crops. However, a comprehensive study of this compound revealed serious adverse effects and showed that it was highly hazardous substance. A systematic review summarizing the results of a number of independent studies is presented in [1, 2]. Carbendazim exhibits toxicity even at low doses, affecting liver cells and causing changes in hematological and biochemical parameters in rats [3]. Benomyl and its metabolite carbendazim were found to have repro