title: Interaction of Eu(III) with mammalian cells: Cytotoxicity, uptake, and speciation as a function of Eu(III) concentration and nutrient composition.
abstract: In case of the release of lanthanides and actinides into the environment, knowledge about their behavior in biological systems is necessary to assess and prevent adverse health effects for humans. We investigated the interaction of europium with FaDu cells (human squamous cell carcinoma cell line) combining analytical methods, spectroscopy, and thermodynamic modeling with in-vitro cell experiments under defined conditions. Both the cytotoxicity of Eu(III) onto FaDu cells and its cellular uptake are mainly concentration-dependent. Moreover, they are governed by its chemical speciation in the nutrient medium. In complete cell culture medium, i.e., in the presence of fetal bovine serum, Eu(III) is stabilized in solution in a wide concentration range by complexation with serum proteins resulting in low cytotoxicity and cellular Eu(III) uptake. In serum-free medium, Eu(III) precipitates as hardly soluble phosphate species, exhibiting a significantly higher cytotoxicity and slightly higher cellular uptake. The presence of a tenfold excess of citrate in serum-free medium causes the formation of Eu(HCit)2(3-) complexes in addition to the dominating Eu(III) phosphate species, resulting in a decreased Eu(III) cytotoxicity and cellular uptake. The results of this study underline the crucial role of a metal ion's speciation for its toxicity and bioavailability.
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Resource Ecology, Bautzner Landstraße 400, 01328 Dresden, Germany. Electronic address: s.sachs@hzdr.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Sachs
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Resource Ecology, Bautzner Landstraße 400, 01328 Dresden, Germany. Electronic address: a.heller@hzdr.de.
authors.forename: Anne
authors.initials: A
authors.lastname: Heller
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Resource Ecology, Bautzner Landstraße 400, 01328 Dresden, Germany. Electronic address: s.weiss@hzdr.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Weiss
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Resource Ecology, Bautzner Landstraße 400, 01328 Dresden, Germany. Electronic address: f.bok@hzdr.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Bok
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Resource Ecology, Bautzner Landstraße 400, 01328 Dresden, Germany. Electronic address: g.bernhard@hzdr.de.
authors.forename: Gert
authors.initials: G
authors.lastname: Bernhard
mesh_terms: D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019343:Citric Acid / Q000737:chemistry; D003470:Culture Media / Q000737:chemistry; D005063:Europium / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D012995:Solubility
chemical_list: D003470:Culture Media; D019343:Citric Acid; D005063:Europium
keywords: Actinides; FaDu cells; Lanthanides; Speciation; TRLFS; Toxicology