title: Differing cytotoxicity and bioavailability of selenite, methylselenocysteine, selenomethionine, selenosugar 1 and trimethylselenonium ion and their underlying metabolic transformations in human cells.
abstract: The trace element selenium (Se) is an integral component of our diet. However, its metabolism and toxicity following elevated uptake are not fully understood. Since the either adverse or beneficial health effects strongly depend on the ingested Se species, five low molecular weight species were investigated regarding their toxicological effects, cellular bioavailability and species-specific metabolism in human cells.
  
  
  
  For the first time, the urinary metabolites methyl-2-acetamido-2-deoxy-1-seleno-β-D-galactopyranoside (selenosugar 1) and trimethylselenonium ion (TMSe) were toxicologically characterised in comparison to the food relevant species methylselenocysteine (MeSeCys), selenomethionine (SeMet) and selenite in human urothelial, astrocytoma and hepatoma cells. In all cell lines selenosugar 1 and TMSe showed no cytotoxicity. Selenite, MeSeCys and SeMet exerted substantial cytotoxicity, which was strongest in the urothelial cells. There was no correlation between the potencies of the respective toxic effects and the measured cellular Se concentrations. Se speciation indicated that metabolism of the respective species is likely to affect cellular toxicity.
  
  
  
  Despite being taken up, selenosugar 1 and TMSe are non-cytotoxic to urothelial cells, most likely because they are not metabolically activated. The absent cytotoxicity of selenosugar 1 and TMSe up to supra-physiological concentrations, support their importance as metabolites for Se detoxification.
authors.affiliation: Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
authors.forename: Talke Anu
authors.initials: TA
authors.lastname: Marschall
authors.affiliation: Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Bornhorst
authors.affiliation: Institute of Chemistry-Analytical Chemistry, University of Graz, Graz, Austria.
authors.forename: Doris
authors.initials: D
authors.lastname: Kuehnelt
authors.affiliation: Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schwerdtle
mesh_terms: D001682:Biological Availability; D045744:Cell Line, Tumor; D056945:Hep G2 Cells; D006801:Humans; D057230:Limit of Detection; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020887:Selenious Acid / Q000493:pharmacokinetics*; D018036:Selenium Compounds / Q000493:pharmacokinetics*; D017279:Selenocysteine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D012645:Selenomethionine / Q000493:pharmacokinetics*; D019459:Urothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D018036:Selenium Compounds; D017279:Selenocysteine; D012645:Selenomethionine; D020887:Selenious Acid; C003717:trimethylselenonium; C002979:selenomethylselenocysteine
keywords: Cellular bioavailability; ICP-QQQ-MS; Selenosugar 1; Small selenium species; Speciation