The study of primary DNA damage in the bone marrow of mice under the combined action of pesticides

Abstract

Introduction. The study of the potential negative effects of combinations of several pesticide active ingredients is an important and understudied area of toxicological and hygienic research. The initial phase of the genotoxicant action on the genetic structures in cells is the primary DNA damage, the identification of which makes it possible to assess the early stages of the genotoxic effect of xenobiotics and their mixtures. The DNA comet assay is widely used for these purposes. The aim of the research is to assess the primary DNA damage under the combined action of pesticides. Materials and methods. To assess DNA damage the experiments on CD-1 mice of both sexes were performed using alkaline comet analysis. The concentration of active products reacting with thiobarbituric acid (TBA) in the blood serum of white outbred rats was assessed as a marker of lipid peroxidation. Results. It was found that mixtures of 2,4-D-acid + glyphosate and thiram + carbendazim did not cause the formation of breaks and alkali-labile sites in the DNA of mice bone marrow cells. Exposure to the combination of the technical grade active ingredients captan and fludioxonil induced the breaks and alkali-labile sites in the DNA of animal bone marrow cells. The comparison of the genotoxicity assessment results obtained by the comet assay and results of analysis of the TBA-active product concentrations in the rat blood serum suggests that the observed primary DNA damage upon exposure to the captan and fludioxonil combination can be mediated by the induction of lipid peroxidation and subsequent interaction of the resulting products with nucleic acids. Conclusion. The results indicate that some pesticides in combination can damage hereditary material in mammalian cells. Therefore, in order to ensure the safe use of pesticides for public health it is necessary to take into account the data on the genotoxicity not only of individual pesticide technical grade active ingredients but also their combinations.