title: Study of commonly used organophosphate pesticides that induced oxidative stress and apoptosis in peripheral blood lymphocytes of rats.
abstract: In a previous study, we have found that organophosphate (OP) pesticides such as chlorpyrifos (CPF), methyl parathion (MPT), and malathion (MLT) significantly induced genotoxicity in peripheral blood lymphocytes of rats. To explore the mechanism of OP-induced genotoxicity, we measured the formation of DNA interstrand cross-links (DICs) and apoptosis in peripheral blood lymphocytes of rats. Peripheral blood lymphocytes of rats were treated with CPF, MPT, and MLT individually and in combination at concentrations of 0.1 and 0.25 LC50for 2, 4, 8, and 12 h at 37°C. Lipid peroxidation (LPO) was measured as a biomarker of oxidative stress. Apoptosis induced by CPF, MPT, and MLT individually and in combination was determined by measuring the intracellular level of active caspase-3 and caspase-9 by spectrofluorimetry. We found significant dose- and time-dependent increases in LPO, DICs formation and increase of intracellular active caspase-3 and caspase-9 in exposed peripheral blood lymphocytes of rats. These findings suggest that the studied pesticides have potential to induce oxidative stress, cause DNA adduct formation, and cause failure of adduct repair, which leads to apoptosis that is partially mediated by activation of intracellular caspase-3 and caspase-9.
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: A
authors.initials: A
authors.lastname: Ojha
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Y K
authors.initials: YK
authors.lastname: Gupta
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D010755:Organophosphates / Q000737:chemistry / Q000633:toxicity*; D009943:Organophosphorus Compounds; D018384:Oxidative Stress / Q000187:drug effects*; D010575:Pesticides / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010755:Organophosphates; D009943:Organophosphorus Compounds; D010575:Pesticides; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9
keywords: DNA adduct; apoptosis; caspases; lipid peroxidation; oxidative stress