Evaluation of DNA damage and cytotoxicity induced by three commonly used organophosphate pesticides individually and in mixture, in rat tissues.

Organophosphate pesticides are among the most widely used synthetic chemicals for controlling a wide variety of pests. Chlorpyrifos (CPF), methyl parathion (MPT), and malathion (MLT) are among the most extensively used organophosphate (OP) pesticides. The main target of action of OP compounds is the central and peripheral nervous system, although it has also been postulated that these compounds in both acute and chronic intoxication, disturb the redox processes and thus induce oxidative stress. The excessive generation of reactive oxygen species (ROS) causes damage to all vital macromolecules including lipids, proteins, and DNA. This study was aimed to investigate the genotoxicity and cytotoxicity of CPF, MPT, and MLT when given singly or in combination. The DNA damage was measured by alkaline single-cell gel electrophoresis or comet assay and expressed as DNA damage index. The results showed that both acute and chronic exposure with CPF, MPT, and MLT, caused significantly marked DNA damage in rat tissues namely, liver, brain, kidney, and spleen, when measured 24 hour posttreatment. It was also observed that MPT caused highest level of DNA damage and brain was maximally affected by these OP compounds. When these pesticides were given in mixture, the damage was not the sum of damage caused by individual pesticide, confirming that these pesticides do not potentiate the toxicity of each other. When the DNA damage was measured 48 and 72 hour posttreatment, the damage was partially repaired. Pesticide exposure also caused histopathological changes in rat tissues.

Genotoxic Potential of Reactive Oxygen Species (Ros), Lipid Peroxidation and DNA Repair Enzymes (Fpg and Endo III) in Alloxan Injected Diabetic Rats.

Diabetes is a chronic metabolic syndrome due to insulin deficiency and is associated with increased oxidative stress in vivo. Oxidative stress including, increased production of reactive oxygen species (ROS) in vivo, can lead to cellular biomolecule damage. Such damage has been suggested to contribute to the pathogenesis of diabetes mellitus. Genotoxicity induced by ROS in diabetic rats, was estimated by measuring DNA single strand breaks and double strand breaks by standard comet assay/ single cell gel electrophoresis (SCGE). To find out whether DNA lesions were caused due to oxidative stress, combination of bacterial DNA repair enzymes which convert base damage to breaks are used. Formamidoaminopyrimidine glycosylase (Fpg) and Endonuclese (Endo III)] recognize oxidized purines and oxidized pyrimidines, respectively, were used in modified comet assay. Significant increase in DNA strand breaks in terms of DNA damage index were observed in diabetic rat lymphocytes in modified comet assay. The involvement of oxidative stress was also examined by estimation of thiobarbituric acid reactive substances (TBARS) in diabetic rats. The levels of TBARS, reactive oxygen species (ROS) namely, hydrogen peroxide, superoxide and nitrate/nitrite anion were also increased in diabetic rats that further shows the involvement of oxidative stress in ROS induced DNA damage. The results of the present study show genotoxic potential of ROS in diabetic rats.