title: DNA damage and methylation induced by glyphosate in human peripheral blood mononuclear cells (in vitro study).
abstract: Glyphosate is a very important herbicide that is widely used in the agriculture, and thus the exposure of humans to this substance and its metabolites has been noted. The purpose of this study was to assess DNA damage (determination of single and double strand-breaks by the comet assay) as well as to evaluate DNA methylation (global DNA methylation and methylation of p16 (CDKN2A) and p53 (TP53) promoter regions) in human peripheral blood mononuclear cells (PBMCs) exposed to glyphosate. PBMCs were incubated with the compound studied at concentrations ranging from 0.1 to 10 mM for 24 h. The study has shown that glyphosate induced DNA lesions, which were effectively repaired. However, PBMCs were unable to repair completely DNA damage induced by glyphosate. We also observed a decrease in global DNA methylation level at 0.25 mM of glyphosate. Glyphosate at 0.25 mM and 0.5 mM increased p53 promoter methylation, while it did not induce statistically significant changes in methylation of p16 promoter. To sum up, we have shown for the first time that glyphosate (at high concentrations from 0.5 to 10 mM) may induce DNA damage in leucocytes such as PBMCs and cause DNA methylation in human cells.
authors.affiliation: Department of Biophysics of Environmental Pollution, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland. Electronic address: m.n.kwiatkowska@wp.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Kwiatkowska
authors.affiliation: Department of Molecular Genetics and Epigenetics, Nofer Institute of Occupational Medicine, Lodz, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Reszka
authors.affiliation: Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Woźniak
authors.affiliation: Department of Molecular Genetics and Epigenetics, Nofer Institute of Occupational Medicine, Lodz, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Jabłońska
authors.affiliation: Department of Biophysics of Environmental Pollution, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors.forename: Jaromir
authors.initials: J
authors.lastname: Michałowicz
authors.affiliation: Department of Biophysics of Environmental Pollution, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors.forename: Bożena
authors.initials: B
authors.lastname: Bukowska
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D019175:DNA Methylation / Q000187:drug effects; D005998:Glycine / Q000031:analogs & derivatives* / Q000633:toxicity; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000097797:Glyphosate
chemical_list: D005998:Glycine; D006540:Herbicides; D000097797:Glyphosate
keywords: DNA damage; DNA methylation; Epigenetic alterations; Glyphosate; Human peripheral blood mononuclear cells