title: Evaluation of genome damage and its relation to oxidative stress induced by glyphosate in human lymphocytes in vitro.
abstract: In the present study we evaluated the genotoxic and oxidative potential of glyphosate on human lymphocytes at concentrations likely to be encountered in residential and occupational exposure. Testing was done with and without metabolic activation (S9). Ferric-reducing ability of plasma (FRAP), thiobarbituric acid reactive substances (TBARS) and the hOGG1 modified comet assay were used to measure glyphosate's oxidative potential and its impact on DNA. Genotoxicity was evaluated by alkaline comet and analysis of micronuclei and other nuclear instabilities applying centromere probes. The alkaline comet assay showed significantly increased tail length (20.39 microm) and intensity (2.19%) for 580 microg/ml, and increased tail intensity (1.88%) at 92.8 microg/ml, compared to control values of 18.15 mum for tail length and 1.14% for tail intensity. With S9, tail length was significantly increased for all concentrations tested: 3.5, 92.8, and 580 microg/ml. Using the hOGG1 comet assay, a significant increase in tail intensity was observed at 2.91 microg/ml with S9 and 580 microg/ml without S9. Without S9, the frequency of micronuclei, nuclear buds and nucleoplasmic bridges slightly increased at concentrations 3.5 microg/ml and higher. The presence of S9 significantly elevated the frequency of nuclear instabilities only for 580 microg/ml. FRAP values slightly increased only at 580 microg/ml regardless of metabolic activation, while TBARS values increased significantly. Since for any of the assays applied, no clear dose-dependent effect was observed, it indicates that glyphosate in concentrations relevant to human exposure do not pose significant health risk.
authors.affiliation: Institute for Medical Research and Occupational Health, Zagreb 10000, Croatia.
authors.forename: Marin
authors.initials: M
authors.lastname: Mladinic
authors.forename: Suzana
authors.initials: S
authors.lastname: Berend
authors.forename: Ana Lucic
authors.initials: AL
authors.lastname: Vrdoljak
authors.forename: Nevenka
authors.initials: N
authors.lastname: Kopjar
authors.forename: Bozica
authors.initials: B
authors.lastname: Radic
authors.forename: Davor
authors.initials: D
authors.lastname: Zeljezic
mesh_terms: D001711:Biotransformation; D020552:Comet Assay; D015894:Genome, Human; D005998:Glycine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D006540:Herbicides / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D018384:Oxidative Stress; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D000097797:Glyphosate
chemical_list: D005998:Glycine; D006540:Herbicides; D017392:Thiobarbituric Acid Reactive Substances; D000097797:Glyphosate