The role of oxidative stress in the in vitro induction of micronuclei by pesticides in mouse lung fibroblasts.
The involvement of the antioxidant enzymes catalase and glutathione peroxidase (both at 0.1 mg/ml) in defence against the genotoxicity of phosphamidon (80 microg/ml) and dieldrin (25 microM) was investigated in order to demonstrate that the two pesticides damage DNA through the generation of reactive oxygen species and therefore of oxidative stress. The pesticide genotoxicity was determined by the cytokinesis-block micronucleus test performed on primary mouse lung fibroblast cultures. Also, 3-aminotriazole (40 mM) and mercaptosuccinate (0.5 mM), inhibitors of catalase and glutathione peroxidase, respectively, were added to the cultures. Data indicate that catalase causes a decrease only in the damage induced by phosphamidon, while glutathione peroxidase protects against damage induced by both phosphamidon and dieldrin. Simultaneous treatment with antioxidant inhibitors and pesticides results in a decrease in micronucleus frequency and cell number, due to apoptotic death. Our results indicate that clastogenic DNA damage produced by the two pesticides is modulated by antioxidant enzymes and their inhibitors and thus could be due to oxidative stress induction.
Cicchetti
Rosadele
R
Department of Public Health and Cell Biology, University of Rome 'Tor Vergata', Via Montpellier 1, I-00133 Rome, Italy. cicchetti@med.uniroma2.it
Argentin
Gabriella
G
D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004249:DNA Damage; D004026:Dieldrin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D015162:Micronucleus Tests; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress; D010575:Pesticides / Q000494:pharmacology*; D010707:Phosphamidon / Q000494:pharmacology; D017382:Reactive Oxygen Species; D004113:Succimer / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D000975:Antioxidants; D004791:Enzyme Inhibitors; D010575:Pesticides; D017382:Reactive Oxygen Species; D010707:Phosphamidon; C060658:dimethyl mercaptosuccinate; D004113:Succimer; D002374:Catalase; D005979:Glutathione Peroxidase; D004026:Dieldrin; D000640:Amitrole