Metabolomics identifies a biological response to chronic low-dose natural uranium contamination in urine samples

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.     

Effects of ionizing radiation on the activity of the major hepatic enzymes implicated in bile acid biosynthesis in the rat

In the days following high-dose radiation exposure, damage to small intestinal mucosa is aggravated by changes in the bile acid pool reaching the gut. Intestinal bile acid malabsorption, as described classically, may be associated with altered hepatic bile acid biosynthesis, which was the objective of this work. The activity of the main rate-limiting enzymes implicated in the bile acid biosynthesis were evaluated in the days following an 8-Gy gamma(60)Co total body irradiation of rats, with concomitant determination of biliary bile acid profiles and intestinal bile acid content. Modifications of biliary bile acid profiles, observed as early as the first post-irradiation day, were most marked at the third and fourth day, and resulted in an increased hydrophobicity index. In parallel, the intestinal bile acids' content was enhanced and hepatic enzymatic activities leading to bile acids were changed. A marked increase of sterol 12 alpha-hydroxylase and decrease of oxysterol 7 alpha-hydroxylase activity was observed at day 3, whereas both cholesterol 7 alpha-hydroxylase and oxysterol 7 alpha-hydroxylase activities were decreased at day 4 after irradiation. These results show, for the first time, radiation-induced modifications of hepatic enzymatic activities implicated in bile acid biosynthesis and suggest that they are mainly a consequence of radiation-altered intestinal absorption, which induces a physiological response of the enterohepatic bile acid recirculation.     

Influence of depleted uranium on hepatic cholesterol metabolism in apolipoprotein E-deficient mice

Depleted uranium (DU) is uranium with a lower content of the fissile isotope U-235 than natural uranium. It is a radioelement and a waste product from the enrichment process of natural uranium. Because of its very high density, it is used in the civil industry and for military purposes. DU exposure can affect many vital systems in the human body, because in addition to being weakly radioactive, uranium is a toxic metal. It should be emphasized that, to be exposed to radiation from DU, you have to eat, drink, or breathe it, or get it on your skin. This particular study is focusing on the health effects of DU for the cholesterol metabolism. Previous studies on the same issue have shown that the cholesterol metabolism was modulated at molecular level in the liver of laboratory rodents contaminated for nine months with DU. However, this modulation was not correlated with some effects at organs or body levels. It was therefore decided to use a "pathological model" such as hypercholesterolemic apolipoprotein E-deficient laboratory mice in order to try to clarify the situation. The purpose of the present study is to assess the effects of a chronic ingestion (during 3 months) of a low level DU-supplemented water (20 mg L(-1)) on the above mentioned mice in order to determine a possible contamination effect. Afterwards the cholesterol metabolism was studied in the liver especially focused on the gene expressions of cholesterol-catabolising enzymes (CYP7A1, CYP27A1 and CYP7B1), as well as those of associated nuclear receptors (LXRα, FXR, PPARα, and SREBP 2). In addition, mRNA levels of other enzymes of interest were measured (ACAT 2, as well as HMGCoA Reductase and HMGCoA Synthase). The gene expression study was completed with SRB1 and LDLr, apolipoproteins A1 and B and membrane transporters ABC A1, ABC G5. The major effect induced by a low level of DU contamination in apo-E deficient mice was a decrease in hepatic gene expression of the enzyme CYP7B1 (-23%) and nuclear receptors LXRα (-24%), RXR (-32%), HNF4α (-21%) when compared to unexposed ones. These modifications on cholesterol metabolism did not lead to increased disturbances that are specific for apolipoprotein E-deficient mice, suggesting that chronic DU exposure did not worsen the pathology in this experimental model. In conclusion, the results of this study indicate that even for a sensitive pathologic model the exposure to a low dose of DU has no relevant impact. The results confirm the results of our first study carried out on healthy laboratory rodents where a sub-chronic contamination with low dose DU did not affect in vivo the metabolism of cholesterol.     

Synthesis and structural study of a fully protected α-C-galactosyl model dipeptide

Summary The synthesis of three N-alkyl-6,7-dideoxy-1,2:3,4-di-O-isopropylidene-7-[(alkyl-carbonyl)amino]-L-glycero-α-D-galacto-octopyranuronamides6a-c, analogous model dipeptides containing two amide groups connected to the α-carbon bearing the fully protected galactose as a side chain, has been realized with the aim of determining the conformational influence of the galactosyl moiety on the peptide backbone. Molecular modeing of6a, X-ray crystallography of6c and IR and NMR experiments on6a-c in organic solvents show that the carbohydrate ring assumes a twist boat conformation. In non-polar organic solvents, the NH of the left amide group interacts with one ketal oxygen of the galactosyl group.     

L'utilisation d'une maladie a virus comme méthode de lutte biologique contrePieris brassicae L.

Summary A virus disease of the ?granulosis? type was encountered by us in laboratoryreared caterpillars ofPieris brassicae L. This disease was first seen byPaillot (1924–25) and the virus was recently described byVago, Lépine andCroissant (1955). Extraction of the granules was made in the laboratory and a series of tests was designed to know the possibility of inducing the disease in healthy caterpillars (no attempt was made to determine the median lethal dose). After a first series of successful laboratory experiments an application was made in the field. (in La Crau — Var). Caterpillars of the last three instars were treated (in the beginning of December 1955) with a suspension prepared by grinding dead cabbageworms. A portable automatic compressed air sprayer was used and a non germicide wetting agent was added. Typical signs of the disease appeared three weeks after treatment and death of the caterpillars occured within a period of ten days. In laboratory tests, when treated caterpillars matured to adults, the butterflies laid fertile eggs but a high percentage of first instar larvae died of the disease. The success of the field tests is encouraging to continue the study of a possible use of virus diseases as means of Biological Control of pests.

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I.N.R.A., Laboratoire de biocénotique et de lutte biologique de La Minière.     

Identification of Glucosinolates in Seeds of Three Brassicaceae Species Known to Hyperaccumulate Heavy Metals

Plants from the Brassicaceae family are known to contain secondary metabolites called glucosinolates. Our goal was to establish by LC/MS the glucosinolate profile of seeds of three Brassicaceae species known to hyperaccumulate heavy metals. We investigated Alyssum fallacinum auct. non Hausskn ., Iberis intermedia Guers ., and Noccaea caerulescens (J. Presl & C. Presl ) F. K. Mey . Our results indicate that A. fallacinum seeds contain glucoiberin and glucoibervirin, which had not been previously identified in this plant. Furthermore, we report for the first time the presence of glucoiberin, glucoibervirin, glucotropaeolin, and sinigrin in I. intermedia. We have detected for the first time glucoconringiin in N. caerulescens. In addition, glucosinalbin, 4‐hydroxyglucobrassicin, and glucomoringin were also detected.     

Colour-scent associations in a tropical orchid: three colours but two odours

Colour and scent are the major pollinator attractants to flowers, and their production may be linked by shared biosynthetic pathways. Species with polymorphic floral traits are particularly relevant to study the joint evolution of floral traits. We used in this study the tropical orchid Calanthe sylvatica from Réunion Island. Three distinct colour varieties are observed, presenting lilac, white or purple flowers, and named respectively C. sylvaticavar.lilacina (hereafter referred as var. lilacina), C. sylvaticavar. alba (var. alba) and C. sylvatica var. purpurea (var. purpurea). We investigated the composition of the floral scent produced by these colour varieties using the non-invasive SPME technique in the wild. Scent emissions are dominated by aromatic compounds. Nevertheless, the presence of the terpenoid (E)-4,8-dimethylnona-1,3,7-triène (DMNT) is diagnostic of var. purpurea, with the volatile organic compounds (VOC) produced by some individuals containing up to 60% of DMNT. We evidence specific colour-scent associations in C. sylvatica, with two distinct scent profiles in the three colour varieties: the lilacina-like profile containing no or very little DMNT (<2%) and the purpurea-like profile containing DMNT (>2%). Calanthe sylvatica var. alba individuals group with one or the other scent profile independently of their population of origin. We suggest that white-flowered individuals have evolved at least twice, once from var. lilacina and at least once from var. purpurea after the colonisation of la Réunion. White-flowered individuals may have been favoured by the particular pollinator fauna characterising the island. These flowering varieties of C. sylvatica, which display three colours but two scents profiles prove that colour is not always a good indicator of odour and that colour-scent associations may be complex, depending on pollination ecology of the populations concerned.     

Les possibilités de l'application des germes pathogènes dans la lutte contre les chenilles défoliatrices

Résumé L'utilisation des germes pathogènes est une solution du problème de la sélectivité. Des solutions concurrentes existent avec certains pesticides chimiques. L'utilisation des germes pathogènes est donc envisagée d'une manière pragmatique en négligeant les problèmes de recherches fondamentales. Pour cette raison les mycoses et les protozoonoses ne sont pas retenues. Les viroses offrent un exemple de la plus grande spécificité d'action. L'application des virus d'insectes a été surtout développée en sylviculture. Une grande difficulté est la multiplication des virus sur organismes vivants. Les bactérioses peuvent être seules retenues pour l'agriculture et l'arboriculture intensives: elles ont un spectre d'action assez étendu mais suffisamment sélectif; les bactéries qui nous intérresent peuvent être multipliées industriellement. Le statut deBacillus thuringiensis Berliner et les propriétés des préparations commerciales ont fait l'objet de développements récents. Dans une revue critique des applications de ces préparations en arboriculture fruitière, on considère d'abord le cas des Mineuses et des Tordeuses. Presque toutes ces chenilles sont susceptibles àB. thuringiensis. Mais la difficulté d'utilisation des préparations est de nature éthologique. De bons résultats sont obtenus au Canada contreArgyrotaenia et en U.R.S.S. contreHyponomcuta. En U.R.S.S. on utilise des produits mixtes à concentration réduite (0,5%) de préparation bactérienne et à concentration extrêmement faible (0,002%) de D.D.T. Les résultats contre le Carpocapse sont négatifs. Les résultats contre les chenilles défoliatrices sont très satisfaisants: en Hollande et au Canada contreMalacosoma; au Canada contre les Géométrides,Operophtera etAlsophila espèces très susceptibles àB. thuringiensis, à la dose de 1 à 2 pounds de préparation (titrant 30×10⁹ spores viables par gramme) pour 100 gallons, soit environ, 1,5%; en France, ces résultats sont confirmés. En conclusion, l'utilisation en verger des prépararations commerciales deBacillus thuringiensis doit être ?intégrée? dans un programme général de protection comprenant à la fois les traitements chimiques et les méthodes culturales. De tels programmes sont actuellement expérimentés dans certains vergers de Pommiers par l'I.P.O. et le T.N.O. en Hollande.