ABSTRACT
Applying the single-cell gel electrophoresis (comet) assay, we show that the widely used organophosphorus pesticide malathion is cytotoxic, genotoxic, and induces oxidative stress in human lymphocytes.
Subject(s)
Cytotoxins/toxicity , Insecticides/toxicity , Lymphocytes/drug effects , Malathion/toxicity , Mutagens/toxicity , Oxidants/toxicity , Acetylcysteine/pharmacology , Antioxidants/pharmacology , Catalase/antagonists & inhibitors , Catalase/metabolism , Comet Assay/methods , Cytotoxins/antagonists & inhibitors , Female , Glutathione Transferase/antagonists & inhibitors , Glutathione Transferase/metabolism , Humans , Insecticides/antagonists & inhibitors , Lipid Peroxidation/drug effects , Lymphocytes/metabolism , Malathion/antagonists & inhibitors , Male , Oxidants/antagonists & inhibitors , Oxidative Stress/drug effects , Primary Cell Culture , Reactive Oxygen Species/agonists , Reactive Oxygen Species/metabolism , Superoxide Dismutase/antagonists & inhibitors , Superoxide Dismutase/metabolism , Young AdultABSTRACT
This study investigates Bisphenol A (BPA) induced oxidative stress that mediates the genotoxicity in in vivo model Drosophila melanogaster. The calculated LC50 for BPA was 12.35 µg/mL. The strains of D. melanogaster were reared in 0.1, 1.0, 2.5 and 5.0 µg/mL BPA treated food media from the embryonic stage (egg); oxidative stress and genotoxicity parameters were analyzed. Food intake analysis confirmed that BPA is not an anti feedant for Drosophila larvae and it consumed BPA containing food. Increased reactive oxygen species (ROS) and lipid peroxidation (LPO) and depletion of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione-s-transferase (GST) antioxidant activities were observed in BPA treated groups compared to control. Positive single spots/wing frequencies were observed in standard (ST) and high bioactivation (HB) crosses of marker heterozygous (MH; mwh/flr3) and balancer heterozygous (BH; mwh/TM3) genotype flies indicating BPA is mutagenic and not recombinogenic. A significant increase in tail length and % tail DNA in Comet assay after BPA treatment reveals that BPA has a potential to induce the genotoxicity. Present study suggests that BPA exposure induces oxidative stress, which could be one of the possible mechanisms for induction of genotoxicity.
Subject(s)
Benzhydryl Compounds/toxicity , Drosophila melanogaster/drug effects , Mutagens/toxicity , Oxidative Stress/drug effects , Phenols/toxicity , Wings, Animal/abnormalities , Animals , Catalase/metabolism , DNA Damage , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Female , Glutathione/metabolism , Glutathione Transferase/metabolism , Larva/drug effects , Larva/genetics , Larva/metabolism , Male , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolismABSTRACT
The mechanism of lead (Pb) modulated heme synthesis pathway induced oxidative stress mediated genotoxicity using standard (ST) and high bioactivation (HB) crosses of Drosophila melanogaster was addressed in the present study. Third instar larvae derived from the ST or HB crosses were reared in sub lethal concentrations of lead acetate (PbAc) treated food media and showed that Pb was readily taken up and accumulated in the said crosses. Pb modulated heme synthesis was evident by significant reductions of δ-aminolevulinic acid dehydratase (δ-ALA-D) and cytochrome P450 (CYP450) and increased accumulation of δ-aminolevulinic acid (δ-ALA). The results have also demonstrated that Pb induced oxidative stress by overproducing reactive oxygen species (ROS) and lipid peroxidation (LPO) and depletion of the antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione-s-transferase (GST). Wing somatic mutation and recombination test (SMART) using ST and HB crosses revealed that Pb is mutagenic and weakly recombinogenic. By employing larval hemocytes, there was an increase in percent of tail DNA in alkaline comet compared to that of neutral comet revealing the DNA single strand breaks were the products of Pb modulated heme synthesis pathway induced oxidative free radicals. Based on these findings, it can be concluded that Pb modulated heme synthesis pathway induces oxidative stress that mediates the genotoxicity in D. melanogaster.
