Estimation of DNA Fragmentation, Mutagenicity and Biochemical Changes in Mice Exposed to Diazinon and Its Commercial Formulation

Diazinon (DZN) (O,O-DiethylO-[4-methyl-6-(propan-2-yl)pyrimidin-2-yl] phosphorothioate) is an organophosphate (OP) insecticide which is the most commonly used to control cockroaches, silverfish, ants, and fleas. It has been extensively used in agriculture (including fruits, vegetables and nut trees) and horticulture for controlling insects in crops allover the world [1]. Commercial diazinon formulations (DZNF)are often more toxic than the pure pesticide compound, as they contain surface active ingredients, dyes, stabilizers, activity enhancers, and organic solvents with unknown or poorly characterized toxicity, which raises concern about the current assessment of genotoxicity induced by this pesticide and calls for a high level of caution in agricultural and household uses [2]. It had been used extensively in home and garden applications, in commercial formulations designed to prevent such pests as crickets or cockroaches from infesting homes or offices, and in pet collars. Residential application methods included aerosol cans, spray equipment, and granular spreaders. Due to the emerging health and ecological risks posed by diazinon, manufacturers agreed to phaseout and cancel all residential products, so its use is minimized (USEPA 2006) [3]. It has been reported that DZN insecticide have negative effects on different tissues and organs such as the liver, brain, cardiac, kidney, pancreas, immune system, reproductive system, and vascular walls and can induce liver toxicity, neurotoxicity, cardiotoxicity, genotoxicity or cytotoxicity, and apoptosis. Various biochemical and hematological adverse changes in the body can be induced by OPcompounds [4]. Moreover, different studies have shown that DZN could induce oxidative damage by increasing the formation of reactive oxygen species (ROS), depletion of the antioxidant enzymes, protein and lipid peroxidation (LPO) and DNA fragmentation in the cells [4,5].

The clastogenic and aneugenic potential of this pesticide was reported, where a significant percentage of chromosome aberrations in bone-marrow cells of the mouse was found [6,7]. Genotoxic effects are considered among the most serious side effects of diazinon which found to increased significantly (P≤0.05) the level of chromosomal aberrations (7.5±1.04) in albino male rats including gap chromosomes (10%), break chromosomes (7%), fragment chromosomes (5%) and deletion chromosomes (8%) [8]. DZNF also induced increases in the frequency of micronucleated (MN) cells and DNA damage inhuman peripheral blood lymphocytes [2].

ALT (alanine aminotransferase) and AST (aspartate aminotransferase) are important indicators of liver damage in clinic finding. These enzymes were secreted to blood in hepatocellular injury and their levels increased [9]. A significant increase in ALT and AST were detected from the 2nd to 4thweek in the DZN-exposed rats [10]. The increased ALT and AST values were also found by Kalender et al., [9], who stated that changes in these enzymes level might differ depending on exposure time and dose in adult male Wistar rats treated orally via gavage for 7 weeks. Organophosphorus insecticides treatment caused an increase in the activities of ALT and AST enzymes in the serum of male and female rats [11, 12]. They concluded that the increase in these enzymes may be due to liver dysfunction and disturbance in the biosynthesis of these enzymes with alteration in the permeability of liver membrane. As well a significant increase of malondialdehyde (MDA) levels in the liver associated with a decrease in antioxidant enzyme was found [11].

Therefore, the present study is designed to assess the effect of DZN and one of its formulations on DNA fragmentation, chromosomal aberrations in both somatic and germ cells and biochemical changes in Swiss albino male mice (Mus musculus).