Soluble Uranium in the Nuclear Cell compartment at Subtoxic Levels

DU Research continues this month in the journal Chemical Research Toxicology.  The research from France exams the effects to human kidney, liver, and neuronal levels.  The work exams neuronal level involvement at subtoxic concentrations.  This methods shows localization in the nucleus and showing its penetration into the cell and opens the door into the mechanism of uranium chemical toxicity.

Chem Res Toxicol. 2010 Nov 10. [Epub ahead of print]

Distribution of Soluble Uranium in the Nuclear Cell Compartment at Subtoxic Concentrations.
Rouas C, Bensoussan H, Suhard D, Tessier C, Grandcolas L, Rebiere F, Dublineau I, Taouis M, Pallardy M, Lestaevel P, Gueguen Y. Institut de RadioProtection et de Sureté Nucléaire, Direction de la Radioprotection de l’Homme, Service de Radiobiologie et d’Epidémiologie, Laboratoire de Radiotoxicologie Expérimentale, BP17, F-92262 Fontenay-aux-Roses, France, Institut de RadioProtection et de Sureté Nucléaire, Direction de la Radioprotection de l’Homme, Service de Dosimétrie Interne, Laboratoire de Radiochimie, BP17, F-92262 Fontenay-aux-Roses, France, UMR 1197 INRA/Université Paris XI, IBAIC, F-91405 Orsay 91405, France, and Universud, INSERM UMR 996 Faculté de pharmacie, F-92296 Châtenay-Malabry, France.

Abstract
Uranium is naturally found in the environment, and its extensive use results in an increased risk of human exposure. Kidney cells have mainly been used as in vitro models to study effects of uranium exposure, and very little about the effects on other cell types is known. The aim of this study was to assess the impact of depleted uranium exposure at the cellular level in human kidney (HEK-293), liver (HepG2), and neuronal (IMR-32) cell lines. Cytotoxicity studies showed that these cell lines reacted in a roughly similar manner to depleted uranium exposure, responding at a cytotoxicity threshold of ∼300-500 μM. Uranium was localized in cells with secondary ion mass spectrometry technology.

Results showed that uranium precipitates at subtoxic concentrations (>100 μM). With this approach, we were able for the first time to observe the soluble form of uranium in the cell at low concentrations (10-100 μM). Moreover, this technique allows us to localize it mainly in the nucleus. These innovative results raise the question of how uranium penetrates into cells and open new perspectives for studying the mechanisms of uranium chemical toxicity.

PMID: 21067124 [PubMed – as supplied by publisher]