title: Genotoxicity of pesticide mixtures present in the diet of the French population.
abstract: Consumers may be simultaneously exposed to several pesticide residues in their diet. A previous study identified the seven most common pesticide mixtures to which the French population was exposed through food consumption in 2006. The aim of this study was to investigate if the seven mixtures are potentially cytotoxic and genotoxic and if so, whether compounds in a same mixture have a combined effect. The cytotoxicity and genotoxicity of the seven mixtures were investigated with a new assay (γ-H2AX) using four human cell lines (ACHN, SH-SY5Y, LS-174T, and HepG2). Mixtures were tested at equimolar concentrations and also at concentrations reflecting their actual proportion in the diet. Irrespective of the cell line tested, parallel cytotoxicity of the seven mixtures was observed. Only one mixture was genotoxic for the HepG2 cells at concentrations = 3 μM in equimolar proportion and at 30 μM in actual proportion. Caspase 3/7 activity, the comet assay, and reactive oxygen species production were also investigated using the same mixture and HepG2 cells. Our results suggest that pesticide metabolites from the mixture generated by HepG2 cells were responsible for the observed damage to DNA. Among the five compounds in the genotoxic mixture, only fludioxonil and cyprodinil were genotoxic for HepG2 cells alone at concentrations = 4 and 20 μM, respectively. Our data suggest a combined genotoxic effect of the mixture at low concentrations with a significantly higher effect of the mixture of pesticides than would be expected from the response to the individual compounds. Environ. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc.
authors.affiliation: Toxalim, Research Centre in Food Toxicology,Toulouse, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Graillot
authors.forename: Natsuko
authors.initials: N
authors.lastname: Takakura
authors.forename: Ludovic Le
authors.initials: LL
authors.lastname: Hegarat
authors.forename: Valerie
authors.initials: V
authors.lastname: Fessard
authors.forename: Marc
authors.initials: M
authors.lastname: Audebert
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cravedi
mesh_terms: D053148:Caspase 3 / Q000032:analysis; D053179:Caspase 7 / Q000032:analysis; D045744:Cell Line, Tumor; D020552:Comet Assay; D045424:Complex Mixtures / Q000737:chemistry / Q000633:toxicity*; D004249:DNA Damage; D004032:Diet / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005506:Food Contamination; D005602:France; D056945:Hep G2 Cells; D006801:Humans; D009152:Mutagenicity Tests; D010573:Pesticide Residues / Q000032:analysis / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000032:analysis
chemical_list: D045424:Complex Mixtures; D010573:Pesticide Residues; D017382:Reactive Oxygen Species; D053148:Caspase 3; D053179:Caspase 7