title: Oral bioavailability of glyphosate: studies using two intestinal cell lines.
abstract: Glyphosate is a commonly used nonselective herbicide that inhibits plant growth through interference with the production of essential aromatic amino acids. In vivo studies in mammals with radiolabeled glyphosate have shown that 34% of radioactivity was associated with intestinal tissue 2 h after oral administration. The aim of our research was to investigate the transport, binding, and toxicity of glyphosate to the cultured human intestinal epithelial cell line, Caco-2, and the rat small intestinal crypt-derived cell line, ileum epithelial cells-18 (IEC-18). An in vitro analysis of the transport kinetics of [14C]-glyphosate showed that 4 h after exposure, approximately 8% of radiolabeled glyphosate moved through the Caco-2 monolayer in a dose-dependent manner. Binding of glyphosate to cells was saturable and approximately 4 x 10(11) binding sites/cell were estimated from bound [14C]. Exposure of Caco-2 cells to > or =10 mg/ml glyphosate reduced transmembrane electrical resistance (TEER) by 82 to 96% and increased permeability to [3H]-mannitol, indicating that paracellular permeability increased in glyphosate-treated cells. At 10-mg/ml glyphosate, both IEC-18 and Caco-2 cells showed disruption in the actin cytoskeleton. In Caco-2 cells, significant lactate dehydrogenase leakage was observed when cells were exposed to 15 mg/ml of glyphosate. These data indicate that at doses >10 mg/ml, glyphosate significantly disrupts the barrier properties of cultured intestinal cells.
authors.affiliation: Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
authors.forename: Luba
authors.initials: L
authors.lastname: Vasiluk
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Pinto
authors.forename: Margo M
authors.initials: MM
authors.lastname: Moore
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001682:Biological Availability; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity*; D006540:Herbicides / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008353:Mannitol / Q000493:pharmacokinetics; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D000097797:Glyphosate
chemical_list: D000199:Actins; D005998:Glycine; D006540:Herbicides; D008353:Mannitol; D000097797:Glyphosate