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.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-013-0544-7) contains supplementary material, which is available to authorized users.

Applying a multiscale systems biology approach to study the effect of chronic low-dose exposure to uranium in rat kidneys

“…For example, in our study, despite the retention of NU in the kidney, no clinical signs related to body weight, food/water consumption, or urine/plasma chemical parameters differentiated the contaminated groups of rats of both sexes from the uncontaminated groups. These observations are consistent with previous studies (Grison et al 2013;Dublineau et al 2014) and demonstrate that clinical parameters do not account for any biological effects at this low level of contamination (concentration in kidney less than 450 ng g À1 for a total radiological dose absorbed less than 0.15 mGy). An important point in health risk evaluation is the easily observed genetic differences between the sexes and between people of different ethnic origins; these must be taken into account when drawing conclusions.…”

“…Moreover, for 1.6 g of kidney mass, the absorbed dose rate in the kidneys of the contaminated rats, was estimated at 9 months of age at 5.4 9 10-7 Gy d-1. Under the maximizing assumption of a constant dose rate over 9 months, the maximum dose absorbed by the kidneys at sacrifice should still be as low as 0.15 mGy and considered as a very low dose of radiological exposure as previously reported (Grison et al 2013).…”

Temporal Effects on Radiation Responses in Nonhuman Primates: Identification of Biofluid Small Molecule Signatures by Gas Chromatography – Mass Spectrometry Metabolomics

“…The compound 5-hydroxyindoleacetic acid is a metabolite of serotonin (5-hydroxytryptamine) formed by aldehyde dehydrogenase via 5hydroxyindoleacetaldehyde and as a possible downstream product of tryptophan metabolism may also be influenced by host microbiota [32,33]. Serotonin has previously received interest as a radioprotector [34,35] and elevated levels of 5-hydroxyindoleacetic acid has been shown in urine after radiation exposure [36][37][38]. Interestingly, kynurenic acid and xanthurenic acid are also metabolic products derived from tryptophan, possible indicators of renal damage, and are commonly detected in urine, as identified in previous radiation metabolomics studies [7].…”

State-of-the-Art Advances in Radiation Biodosimetry for Mass Casualty Events Involving Radiation Exposure

“…In another study of a rat model, a metabolomics approach was used to determine the effects of chronic low-dose internal exposures from ingested natural uranium or 137 Cs. In this system, LC-MS detected metabolomic profiles in serum and urine unique to the internal exposure ( 55 , 56 ).…”