title: Metabolomics identifies a biological response to chronic low-dose natural uranium contamination in urine samples.
abstract: Because uranium is a natural element present in the earth's crust, the population may be chronically exposed to low doses of it through drinking water. Additionally, the military and civil uses of uranium can also lead to environmental dispersion that can result in high or low doses of acute or chronic exposure. Recent experimental data suggest this might lead to relatively innocuous biological reactions. The aim of this study was to assess the biological changes in rats caused by ingestion of natural uranium in drinking water with a mean daily intake of 2.7 mg/kg for 9 months and to identify potential biomarkers related to such a contamination. Subsequently, we observed no pathology and standard clinical tests were unable to distinguish between treated and untreated animals. Conversely, LC-MS metabolomics identified urine as an appropriate biofluid for discriminating the experimental groups. Of the 1,376 features detected in urine, the most discriminant were metabolites involved in tryptophan, nicotinate, and nicotinamide metabolic pathways. In particular,N-methylnicotinamide, which was found at a level seven times higher in untreated than in contaminated rats, had the greatest discriminating power. These novel results establish a proof of principle for using metabolomics to address chronic low-dose uranium contamination. They open interesting perspectives for understanding the underlying biological mechanisms and designing a diagnostic test of exposure.
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM, SRBE, LRTOX, Fontanay-aux-Roses, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Grison
authors.affiliation: Aix Marseille Université, NORT, 13005 Marseille, France.|Inserm, UMR_S 1062, 13005 Marseille, France.|Inra, UMR_INRA 1260, 13005 Marseille, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Favé
authors.affiliation: Aix Marseille Université, NORT, 13005 Marseille, France.|Inserm, UMR_S 1062, 13005 Marseille, France.|Inra, UMR_INRA 1260, 13005 Marseille, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Maillot
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM, SRBE, LRTOX, Fontanay-aux-Roses, France.
authors.forename: Line
authors.initials: L
authors.lastname: Manens
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM, SRBE, LRTOX, Fontanay-aux-Roses, France.
authors.forename: Olivia
authors.initials: O
authors.lastname: Delissen
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM, SDI, LEDI, Fontanay-aux-Roses, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Blanchardon
authors.affiliation: Aix Marseille Université, NORT, 13005 Marseille, France.|Inserm, UMR_S 1062, 13005 Marseille, France.|Inra, UMR_INRA 1260, 13005 Marseille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Banzet
authors.affiliation: Aix Marseille Université, NORT, 13005 Marseille, France.|Inserm, UMR_S 1062, 13005 Marseille, France.|Inra, UMR_INRA 1260, 13005 Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Defoort
authors.affiliation: Aix Marseille Université, NORT, 13005 Marseille, France.|Inserm, UMR_S 1062, 13005 Marseille, France.|Inra, UMR_INRA 1260, 13005 Marseille, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Bott
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM, SRBE, LRTOX, Fontanay-aux-Roses, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dublineau
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM, Fontanay-aux-Roses, France.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Aigueperse
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM, Fontanay-aux-Roses, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Gourmelon
authors.affiliation: Aix Marseille Université, NORT, 13005 Marseille, France.|Inserm, UMR_S 1062, 13005 Marseille, France.|Inra, UMR_INRA 1260, 13005 Marseille, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Martin
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM, SRBE, LRTOX, Fontanay-aux-Roses, France.
authors.forename: Maâmar
authors.initials: M
authors.lastname: Souidi
keywords: Chronic; Low-dose; Metabolomics; N-methylnicotinamide; Uranium; Urine