title: Evidence of isotopic fractionation of natural uranium in cultured human cells.
abstract: The study of the isotopic fractionation of endogen elements and toxic heavy metals in living organisms for biomedical applications, and for metabolic and toxicological studies, is a cutting-edge research topic. This paper shows that human neuroblastoma cells incorporated small amounts of uranium (U) after exposure to 10 µM natural U, with preferential uptake of the235U isotope with regard to238U. Efforts were made to develop and then validate a procedure for highly accurate n(238U)/n(235U) determinations in microsamples of cells. We found that intracellular U is enriched in235U by 0.38 ± 0.13‰ (2σ, n = 7) relative to the exposure solutions. These in vitro experiments provide clues for the identification of biological processes responsible for uranium isotopic fractionation and link them to potential U incorporation pathways into neuronal cells. Suggested incorporation processes are a kinetically controlled process, such as facilitated transmembrane diffusion, and the uptake through a high-affinity uranium transport protein involving the modification of the uranyl (UO22+) coordination sphere. These findings open perspectives on the use of isotopic fractionation of metals in cellular models, offering a probe to track uptake/transport pathways and to help decipher associated cellular metabolic processes.
authors.affiliation: Den-Service d'Etudes Analytiques et de Réactivité des Surfaces (SEARS), Commissariat à l'Energie Atomique et aux Énergies Alternatives (CEA), Université Paris-Saclay, F-91191 Gif sur Yvette, France; edes.PAREDES-PAREDES@cea.fr carole.bresson@cea.fr.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Paredes
authors.affiliation: CEA, Direction de la Recherche Fondamentale (DRF), Biosciences and Biotechnologies Institute (BIAM), F-30207 Bagnols-sur-Cèze, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Avazeri
authors.affiliation: CEA, Direction de la Recherche Fondamentale (DRF), Biosciences and Biotechnologies Institute (BIAM), F-30207 Bagnols-sur-Cèze, France.|CEA, CNRS, Aix-Marseille Université, UMR 7265, Biologie Végétale et Microbiologie Environnementales, Laboratoire des Interactions Protéine Métal, F-13108 Saint-Paul-lez-Durance, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Malard
authors.affiliation: CEA, Direction de la Recherche Fondamentale (DRF), Biosciences and Biotechnologies Institute (BIAM), F-30207 Bagnols-sur-Cèze, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Vidaud
authors.affiliation: Den-Service d'Etudes Analytiques et de Réactivité des Surfaces (SEARS), Commissariat à l'Energie Atomique et aux Énergies Alternatives (CEA), Université Paris-Saclay, F-91191 Gif sur Yvette, France.
authors.forename: Pascal E
authors.initials: PE
authors.lastname: Reiller
authors.affiliation: Université de Bordeaux, Centre d'Etudes Nucléaires de Bordeaux Gradignan (CENBG), UMR 5797, F-33170 Gradignan, France.|CNRS, Institut National de Physique Nucléaire et de Physique des Particules (IN2P3), CENBG, UMR 5797, F-33170 Gradignan, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Ortega
authors.affiliation: Den-Service d'Etudes Analytiques et de Réactivité des Surfaces (SEARS), Commissariat à l'Energie Atomique et aux Énergies Alternatives (CEA), Université Paris-Saclay, F-91191 Gif sur Yvette, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Nonell
authors.affiliation: Den-Service d'Etudes Analytiques et de Réactivité des Surfaces (SEARS), Commissariat à l'Energie Atomique et aux Énergies Alternatives (CEA), Université Paris-Saclay, F-91191 Gif sur Yvette, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Isnard
authors.affiliation: Den-Département de Physico-Chimie (DPC), CEA, Université Paris-Saclay, F-91191 Gif sur Yvette, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chartier
authors.affiliation: Den-Service d'Etudes Analytiques et de Réactivité des Surfaces (SEARS), Commissariat à l'Energie Atomique et aux Énergies Alternatives (CEA), Université Paris-Saclay, F-91191 Gif sur Yvette, France; edes.PAREDES-PAREDES@cea.fr carole.bresson@cea.fr.
authors.forename: Carole
authors.initials: C
authors.lastname: Bresson
mesh_terms: D018929:Cell Culture Techniques; D002460:Cell Line / Q000378:metabolism; D005591:Chemical Fractionation / Q000379:methods*; D006801:Humans; D007554:Isotopes; D009474:Neurons / Q000378:metabolism; D014501:Uranium / Q000032:analysis* / Q000378:metabolism
chemical_list: D007554:Isotopes; D014501:Uranium
keywords: analytical procedure development; isotopic fractionation; microsamples; neuronal cells; uranium