Uranium uptake is mediated markedly by clathrin-mediated endocytosis and induce dose-dependent toxicity in HK-2 cells.

The objective of this study was to explore the endocytosis mechanisms of uranium uptake in HK-2 cells and its toxic effects. Our results demonstrated that uranium exposure impairs redox homeostasis and increases the permeability of the cell membrane and mitochondrial membrane, which may induce cell apoptosis by cytochrome-c leakage. Alkaline phosphatase activity increased after uranium exposure, which may be involved in the process of intracellular mineralisation of uranium, leading to severe cell necrosis. Furthermore, our findings demonstrated that the clathrin-mediated endocytosis process contributed substantially to uranium uptake in HK-2 cells and the total uranium uptake was highly correlated with cell viability, reaching a high correlation coefficient (r = -0.853) according to Pearson correlation analysis. In conclusion, the uptake of uranium into mammalian cells was mainly facilitated by the clathrin-mediated endocytosis pathway and induced dose-dependent cellular toxicity, including redox homeostasis imbalance, membrane injury, cell apoptosis and necrosis.

Depleted uranium induces thyroid damage through activation of ER stress via the thrombospondin 1-PERK pathway.

Depleted uranium (DU) can cause damage to the body, but its effects on the thyroid are unclear. The purpose of this study was to investigate the DU-induced thyroid damage and its potential mechanism in order to find new targets for detoxification after DU poisoning. A model of acute exposure to DU was constructed in rats. It was observed that DU accumulated in the thyroid, induced thyroid structure disorder and cell apoptosis, and decreased the serum T4 and FT4 levels. Gene screening showed that thrombospondin 1 (TSP-1) was a sensitive gene of DU, and the expression of TSP-1 decreased with the increase of DU exposure dose and time. TSP-1 knockout mice exposed to DU had more severe thyroid damage and lower serum FT4 and T4 levels than wild-type mice. Inhibiting the expression of TSP-1 in FRTL-5 cells aggravated DU-induced apoptosis, while exogenous TSP-1 protein alleviated the decreased viability in FRTL-5 cells caused by DU. It was suggested that DU may caused thyroid damage by down-regulating TSP-1. It was also found that DU increased the expressions of PERK, CHOP, and Caspase-3, and 4-Phenylbutyric (4-PBA) alleviated the DU-induced FRTL-5 cell viability decline and the decrease levels of rat serum FT4 and T4 caused by DU. After DU exposure, the PERK expression was further up-regulated in TSP-1 knockout mice, and the increased expression of PERK was alleviated in TSP-1 over-expressed cells, as well as the increased expression of CHOP and Caspase-3. Further verification showed that inhibition of PERK expression could reduce the DU-induced increased expression of CHOP and Caspase-3. These findings shed light on the mechanism that DU may activate ER stress via the TSP 1-PERK pathway, thereby leading to thyroid damage, and suggest that TSP-1 may be a potential therapeutic target for DU-induced thyroid damage.

Uranium induces kidney cells apoptosis via reactive oxygen species generation, endoplasmic reticulum stress and inhibition of PI3K/AKT/mTOR signaling in culture.

Uranium (U) induces generation of excessive intracellular reactive oxygen species (ROS), which is generally considered as a possible mediator of U-triggered kidney tubular cells injury and nephrotoxicity. Our goal is designed to elucidate that the precise molecular mechanism in ROS downstream is association with U-induced NRK-52E cells apoptosis. The results show that U intoxication in NRK-52E cells reduced cell activity and triggered apoptosis, as demonstrated by flow cytometry and apoptotic marker cleaved Caspase-3 expression. U exposure triggered endoplasmic reticulum (ER) stress, which is involvement of apoptosis determined by marker molecules including GRP78, PERK, IRE1, ATF6, CHOP, cleaved Caspase-12, and Caspase-3. Administration of antioxidant N-acetylcysteine (NAC) effectively blocked U-triggered ROS generation, ER stress, and apoptosis. U contamination evidently decreased the expression of phosphorylation PI3K, AKT, and mTOR and ratios of their respective phosphorylation to the corresponding total proteins. Application of a PI3K activator IGF-1 significantly abolished these adverse effects of U intoxication on PI3K/AKT/mTOR signaling and subsequently abrogated U-triggered apoptosis. NAC also effectively reversed down-regulation of phosphorylated PI3K induced by U exposure. Taken together, these data strongly suggest that U treatment induces NRK-52E cells apoptosis through ROS production, ER stress, and down-regulation of PI3K/AKT/mTOR signaling. Targeting ROS formation-, ER stress-, and PI3K/AKT/mTOR pathway-mediated apoptosis could be a novel approach for attenuating U-triggered nephrotoxicity.

Bifunctional Phosphorylcholine-Modified Adsorbent with Enhanced Selectivity and Antibacterial Property for Recovering Uranium from Seawater.

The recovery of uranium from seawater is of great concern because of the growing demand for nuclear energy. Though amidoxime-functionalized adsorbents as the most promising adsorbents have been widely used for this purpose, their low selectivity and vulnerability to biofouling have limited their application in real marine environments. Herein, a new bifunctional phosphorylcholine-modified adsorbent (PVC-PC) is disclosed. The PVC-PC fiber is found to be suitable for use in the pH range of seawater and metals that commonly coexist with uranium, such as alkali and alkaline earth metals, transition metals, and lanthanide metals, have no obvious effect on its uranium adsorption capacity. PVC-PC shows better selectivity and adsorption capacity than the commonly used amidoxime-functionalized adsorbent. Furthermore, PVC-PC fiber exhibits excellent antibacterial properties which could reduce the effects of biofouling caused by marine microorganisms. Because of its good selectivity and antibacterial property, phosphorylcholine-based material shows great potential as a new generation adsorbent for uranium recovery from seawater.

Isotopic variations of copper at the protein fraction level in neuronal human cells exposed in vitro to uranium.

The study of isotopic variations of endogenous and toxic metals in fluids and tissues is a recent research topic with an outstanding potential in biomedical and toxicological investigations. Most of the analyses have been performed so far in bulk samples, which can make the interpretation of results entangled, since different sources of stress or the alteration of different metabolic processes can lead to similar variations in the isotopic compositions of the elements in bulk samples. The downscaling of the isotopic analysis of elements at the sub-cellular level, is considered as a more promising alternative. Here we present for the first time the accurate determination of Cu isotopic ratios in four main protein fractions from lysates of neuron-like human cells exposed in vitro to 10 µM of natural uranium for seven days. These protein fractions were isolated by Size Exclusion Chromatography and analysed by Multi-Collector Inductively Coupled Plasma Mass Spectrometry to determine the Cu isotopic variations in each protein fraction with regard to the original cell lysate. Values obtained, expressed as δ65Cu, were -0.03 ± 0.14 ‰ (Uc, k = 2), -0.55 ± 0.20 ‰ (Uc, k = 2), -0.32 ± 0.21 ‰ (Uc, k = 2) and +0.84 ± 0.21 ‰ (Uc, k = 2) for the four fractions, satisfying the mass balance. The results obtained in this preliminary study pave the way for dedicated analytical developments to identify new specific disease biomarkers, to gain insight into stress-induced altered metabolic processes, as well as to decipher metabolic pathways of toxic elements.

The nitric oxide suppressed Arabidopsis mutants- Atnoa1 and Atnia1nia2noa1-2 produce nitric oxide in MS growth medium and on uranium exposure.

The mutants Atnoa1 and Atnia1nia2noa1-2 having a defective chloroplast developmental process, showed enhanced chlorophyll levels when they were grown on Murashige and Skoog (MS) medium and on exposure with uranium (U) on Hoagland medium. Thus we hypothesized that these mutants probably produced NO in MS medium and on exposure with U. Wild-type Col-0, Atnoa1, Atnia1nia2noa1-2 plants were cultured on modified Hoagland and 1/10 MS media and NO generation in the roots of these mutants was monitored using NO selective fluorescent dyes, DAF-2DA and Fl2E. Both Atnoa1 and Atnia1nia2noa1-2 triple mutants produced NO as observed by increases in DAF-2T and Fl2E fluorescence when these mutants were grown on MS medium but not on Hoagland medium. In presence of NO scavenger, methylene blue (MB, 200 µM), DAF-2T and Fl2E fluorescence was completely abolished. On the other hand treatment of the plants with 25 µM U triggered NO generation. U-treated Atnoa1 and Atnia1nia2noa1-2 plants upregulated genes (POR B, POR D, CHL D) involved in the chlorophyll biosynthesis. From these results it was concluded that Atnoa1 and Atnia1nia2noa1-2 are conditional NO producers and it appears that NO generation in plants substantially depends on growth medium and NIA1, NIA2 or NOA1 does not appear to be really involved in NO generation in MS medium or after U exposure.

An anti-algae adsorbent for uranium extraction: l-Arginine functionalized graphene hydrogel loaded with Ag nanoparticles.

Uranium (VI) is very essential element in nuclear technique and the enrichment uranium has attracted lots of attention. In this work, l-Arginine and Ag nanoparticles (AgNPs) functionalized reduced graphene oxide ternary hydrogel composites (Ag-l-Arg-rGH) were successfully synthesized, which combined the insertion of AgNPs with one-step thermal reduction and an assembly of graphene oxide nanosheets, using l-Arginine (l-Arg) as both a functional and cross-linking agents. The Ag-l-Arg-rGH composites exhibited great enhanced sorption capacity. Kinetic data best fitted the pseudo-second-order model. The thermodynamic data fitted the Langmuir isotherm model and the calculated maximum adsorption capacity is 434.78 mg/g. In addition, the anti-algae experimental results indicated adsorbent showed marked algal inhibition with the presence of AgNPs in the Ag-l-Arg-rGH composites. In the simulated seawater experiments, The distribution coefficient (Kd) value of uranium(VI) with other competing ions was 2.41 × 104 mL g-1. Thereby, the Ag-l-Arg-rGH composites possessed a promising potential for the enrichment uranium (VI) from nature seawater.

Assessment of Bacterial Community Composition of Anaerobic Granular Sludge in Response to Short-Term Uranium Exposure.

The effect of 10-50 µM uranium (U(VI)) on the bacterial community of anaerobic granular sludge was investigated by 24-h exposure tests, after which the bacterial community was analyzed by high-throughput sequencing. The specific U(VI) reducing activity of the anaerobic granular sludge ranged between 3.1 to 19.7 µM U(VI) g-1(VSS) h-1, independently of the initial U(VI) concentration. Alpha diversity revealed that microbial richness and diversity was the highest for anaerobic granular sludge upon 10 µM uranium exposure. Compared with the original biomass, the phylum of Euryarchaeota was significantly affected, whereas the Bacteroidetes, Firmicutes, and Synergistetes phyla were only slightly affected. However, the abundance of Chloroflexi and Proteobacteria phyla clearly increased after 24 h uranium exposure. Based on the genus level analysis, significant differences appeared in the bacterial abundance after uranium exposure. The proportions of Pseudomonas, Acinetobacter, Parabacteroides, Brevundimonas, Sulfurovum, and Trichococcus increased significantly, while the abundance of Paludibacter and Erysipelotrichaceae incertae sedis decreased dramatically. This study shows a dynamic diversification of the bacterial composition as a response to a short time (24 h) U(VI) exposure (10-50 µM).

Methods for Analyzing the Impacts of Natural Uranium on In Vitro Osteoclastogenesis.

Uranium has been shown to interfere with bone physiology and it is well established that this metal accumulates in bone. However, little is known about the effect of natural uranium on the behavior of bone cells. In particular, the impact of uranium on osteoclasts, the cells responsible for the resorption of the bone matrix, is not documented. To investigate this issue, we have established a new protocol using uranyl acetate as a source of natural uranium and the murine RAW 264.7 cell line as a model of osteoclast precursors. Herein, we detailed all the assays required to test uranium cytotoxicity on osteoclast precursors and to evaluate its impact on the osteoclastogenesis and on the resorbing function of mature osteoclasts. The conditions we have developed, in particular for the preparation of uranyl-containing culture media and for the seeding of RAW 264.7 cells allow to obtain reliable and highly reproductive results. Moreover, we have optimized the use of software tools to facilitate the analysis of various parameters such as the size of osteoclasts or the percentage of resorbed matrix.

Synthesis and structure elucidation of novel salophen-based dioxo-uranium(VI) complexes: In-vitro and in-silico studies of their DNA/BSA-binding properties and anticancer activity.

The synthesis and characterization of three dioxo U(VI) complexes, [UO2(L1)(OH2)], [UO2(L2)DMF], and [UO2(L2)DMSO], [L1]2- = 1,1'-(4-methyl-1,2-phenylenebis (nitrilomethylidyne))di-2-naphtholate: [L2]2- = 1,1'-(o-phenylenebis (nitrilomethylidyne)) di-2-naphtholate, are reported. Elemental analysis, FT-IR, 1HNMR, UV-Vis spectroscopy, molar conductivity and single crystal X-ray diffraction were used to characterize the complexes. It was found that the complexes adopt a distorted pentagonal bipyramidal coordination geometry. The interaction of the synthesized complexes with DNA and bovine serum albumin was thoroughly investigated using both experimental and theoretical studies. UV-Vis absorption and fluorescence quenching techniques were applied to determine the binding parameters as well as the mechanism of the interaction of each complex with DNA and the protein. The results obtained suggested that interaction of the complexes with DNA occurred through partial intercalation into the minor grooves of DNA with binding constants in the range of 0.661 × 105-1.56 × 105 M-1. In addition, interaction of the complexes with bovine serum albumin quenched the fluorescence emission of the tryptophan residues of the protein binding constants and thermodynamic parameters were obtained from the fluorescence quenching experiments at different temperatures. The values of binding constants revealed moderate interactions between the synthesized complexes and the protein suggesting that this protein could act as a suitable vehicle for transportation of the compounds. The results of molecular docking confirmed those of the experimental studies. The anticancer properties of the title complexes were also evaluated through a study of the in vitro cytotoxicity of the compounds against the HT-29 and MCF-7 cancer cell lines and the DPSC normal cell line using an MTT assay.

Uranium and the Central Nervous System: What Should We Learn from Recent New Tools and Findings?

Increasing industrial and military use of uranium has led to environmental pollution, which may result in uranium reaching the brain and causing cerebral dysfunction. A recent literature review has discussed data published over the last 10 years on uranium and its effects on brain function (Dinocourt C, Legrand M, Dublineau I, et al., Toxicology 337:58-71, 2015). New models of uranium exposure during neonatal brain development and the emergence of new technologies (omics and epigenetics) are of value in identifying new specific targets of uranium. Here we review the latest studies of neurogenesis, epigenetics, and metabolic dysfunctions and the identification of new biomarkers used to establish potential pathophysiological states of neurodevelopmental and neurodegenerative diseases.

Effects of uranium concentration on microbial community structure and functional potential.

Located in the Northern Territory of Australia, Ranger uranium mine is directly adjacent to the UNESCO World Heritage listed Kakadu National Park, with rehabilitation targets needed to ensure the site can be incorporated into the park following the mine's closure in 2026. This study aimed to understand the impact of uranium concentration on microbial communities, in order to identify and describe potential breakpoints in microbial ecosystem services. This is the first study to report in situ deployment of uranium-spiked sediments along a concentration gradient (0-4000 mg U kg-1 ), with the study design maximising the advantages of both field surveys and laboratory manipulative studies. Changes to microbial communities were characterised through the use of amplicon and shotgun metagenomic next-generation sequencing. Significant changes to taxonomic and functional community assembly occurred at a concentration of 1500 mg U kg-1 sediment and above. At uranium concentrations of ≥ 1500 mg U kg-1 , genes associated with methanogenic consortia and processes increased in relative abundance, while numerous significant changes were also seen in the relative abundances of genes involved in nitrogen cycling. Such alterations in carbon and nitrogen cycling pathways suggest that taxonomic and functional changes to microbial communities may result in changes in ecosystem processes and resilience.

Diversity, metal resistance and uranium sequestration abilities of bacteria from uranium ore deposit in deep earth stratum.

Metal resistance and uranium (U) sequestration abilities of bacteria residing in subsurface U ore was investigated using 122 pure culture strains isolated through enrichment. The cumulative frequencies of isolates resistant to each metal tested were as follows: As(V), 74%; Zn, 58%; Ni, 53%; Cd, 47%; Cr(VI), 41%; Co, 40%; Cu, 20%; and Hg, 4%. 16S rRNA gene analysis revealed that isolated bacteria belonged to 14 genera with abundance of Arthrobacter, Microbacterium, Acinetobacter and Stenotrophomonas. Cobalt did not interfere with the growth of most of the bacterial isolates belonging to different groups while U allowed growth of four different genera of which Stenotrophomonas and Microbacterium showed high U tolerance. Interestingly, tolerance to Ni, Zn, Cu, and Hg was observed only in Microbacterium, Arthrobacter, Paenibacillus¸ and Acinetobacter, respectively. However, Microbacterium was found to be dominant when isolated from other five different metal enrichments including U. Uranium removal study showed that 84% of the test bacteria could remove more than 50mgUg(-1) dry weight from 80 or 160mgL(-1) U within 48h. In general, Microbacterium, Arthrobacter and Acinetobacter could remove a higher amount of U. High resolution transmission electron microscopy (HRTEM) study of U exposed cells revealed that accumulated U sequestered mostly around the cell periphery. The study highlights that indigenous U ore deposit bacteria have the potential to interact with U, and thus could be applied for bioremediation of U contaminated sites or wastes.

The long-term effect of uranium and pH on the community composition of an artificial consortium.

In the environment, microorganisms are living in diverse communities, which are impacted by the prevailing environmental conditions. Here, we present a study investigating the effect of low pH and elevated uranium concentration on the dynamics of an artificial microbial consortium. The members (Caulobacter sp. OR37, Asinibacterium sp. OR53, Ralstonia sp. OR214 and Rhodanobacter sp. OR444) were isolated from a uranium contaminated and acidic subsurface sediment. In pure culture, Ralstonia sp. OR214 had the highest growth rate at neutral and low pH and only Caulobacter sp. OR37 and Asinibacterium sp. OR53 grew in the presence uranium. The four strains were mixed in equal ratios, incubated at neutral and low pH and in the presence uranium and transferred to fresh medium once per week for 30 weeks. After 30 weeks, Ralstonia sp. OR214 was dominant at low and neutral pH and Caulobacter sp. OR37 and Asinibacterium sp. OR53 were dominant in the presence of uranium. After 12 weeks, the cultures were also transferred to new conditions to access the response of the consortia to changing conditions. The transfers showed an irreversible effect of uranium, but not of low pH on the consortia. Overall, the strains initially tolerant to the respective conditions persisted over time in high abundances in the consortia.

Metals other than uranium affected microbial community composition in a historical uranium-mining site.

To understand the links between the long-term impact of uranium and other metals on microbial community composition, ground- and surface water-influenced soils varying greatly in uranium and metal concentrations were investigated at the former uranium-mining district in Ronneburg, Germany. A soil-based 16S PhyloChip approach revealed 2358 bacterial and 35 archaeal operational taxonomic units (OTU) within diverse phylogenetic groups with higher OTU numbers than at other uranium-contaminated sites, e.g., at Oak Ridge. Iron- and sulfate-reducing bacteria (FeRB and SRB), which have the potential to attenuate uranium and other metals by the enzymatic and/or abiotic reduction of metal ions, were found at all sites. Although soil concentrations of solid-phase uranium were high, ranging from 5 to 1569 µg·g (dry weight) soil(-1), redundancy analysis (RDA) and forward selection indicated that neither total nor bio-available uranium concentrations contributed significantly to the observed OTU distribution. Instead, microbial community composition appeared to be influenced more by redox potential. Bacterial communities were also influenced by bio-available manganese and total cobalt and cadmium concentrations. Bio-available cadmium impacted FeRB distribution while bio-available manganese and copper as well as solid-phase zinc concentrations in the soil affected SRB composition. Archaeal communities were influenced by the bio-available lead as well as total zinc and cobalt concentrations. These results suggest that (i) microbial richness was not impacted by heavy metals and radionuclides and that (ii) redox potential and secondary metal contaminants had the strongest effect on microbial community composition, as opposed to uranium, the primary source of contamination.

Induction of Oxidative Stress and Antioxidative Mechanisms in Arabidopsis thaliana after Uranium Exposure at pH 7.5.

To evaluate the environmental impact of uranium (U) contamination, it is important to investigate the effects of U at ecologically relevant conditions. Since U speciation, and hence its toxicity, strongly depends on environmental pH, the present study aimed to investigate dose-dependent effects of U at pH 7.5. Arabidopsis thaliana plants (Mouse-ear Cress) were exposed for three days to different U concentrations at pH 7.5. In the roots, the increased capacities of ascorbate peroxidase and glutathione reductase indicate an important role for the ascorbate-glutathione cycle during U-induced stress. However, a significant decrease in the ascorbate redox state was observed after exposure to 75 and 100 µM U, indicating that those roots are severely stressed. In accordance with the roots, the ascorbate-glutathione cycle plays an important role in the antioxidative defence systems in A. thaliana leaves exposed to U at pH 7.5 as the ascorbate and glutathione biosynthesis were upregulated. In addition, small inductions of enzymes of the antioxidative defence system were observed at lower U concentrations to counteract the U-induced stress. However, at higher U concentrations it seems that the antioxidative defence system of the leaves collapses as reductions in enzyme activities and gene expression levels were observed.

Synthesis of uranyl(II), vanadyl(II) and zirconyl urate complexes, spectral, thermal and biological studies.

Three urate chelations were obtained when uric acid was reacted with UO2(CH3COO)2H2O, VOSO4·XH2O and ZrOCl2·XH2O salts with neutralized with 0.1 M NaOH aqueous media. The 1:2 metal-to-ligand complexes [(UO2)2(C5H2N4O3)2](H2O), [(ZrO)2(H2O)2(C5H2N4O3)2] and [VO((C5H3N4O3)2] were characterized by elemental analyses, molar conductivity, (infrared, Raman and UV-vis) spectra, effective magnetic moment in Bohr magnetons, and thermal analysis (TG/DTG). The urate ligand coordinates as mononegative bidentate donor towards the mononuclear central vanadium atom and coordinated as binegative tetradentate mode towards the binuclear dioxouranium and zirconyl centers. The antibacterial activity of the metal complexes were tested against some kind of bacteria and fungi strains and compared with uric acid. The ligand, ZrO(II) and UO2(II) complex showed a week potential degradation on calf thymus DNA, whereas VO(II) complex slightly degraded the DNA.

Use of combined microscopic and spectroscopic techniques to reveal interactions between uranium and Microbacterium sp. A9, a strain isolated from the Chernobyl exclusion zone.

Although uranium (U) is naturally found in the environment, soil remediation programs will become increasingly important in light of certain human activities. This work aimed to identify U(VI) detoxification mechanisms employed by a bacteria strain isolated from a Chernobyl soil sample, and to distinguish its active from passive mechanisms of interaction. The ability of the Microbacterium sp. A9 strain to remove U(VI) from aqueous solutions at 4 °C and 25 °C was evaluated, as well as its survival capacity upon U(VI) exposure. The subcellular localisation of U was determined by TEM/EDX microscopy, while functional groups involved in the interaction with U were further evaluated by FTIR; finally, the speciation of U was analysed by TRLFS. We have revealed, for the first time, an active mechanism promoting metal efflux from the cells, during the early steps following U(VI) exposure at 25 °C. The Microbacterium sp. A9 strain also stores U intracellularly, as needle-like structures that have been identified as an autunite group mineral. Taken together, our results demonstrate that this strain exhibits a high U(VI) tolerance based on multiple detoxification mechanisms. These findings support the potential role of the genus Microbacterium in the remediation of aqueous environments contaminated with U(VI) under aerobic conditions.

The pH strongly influences the uranium-induced effects on the photosynthetic apparatus of Arabidopsis thaliana plants.

To study the impact of environmental uranium (U) contamination, effects should be analysed at different environmentally relevant pH levels as the speciation of U, and hence its toxicity, is strongly dependent on the pH. As photosynthesis is a major energy producing process in plants intimately connected to plant growth and known to be susceptible to metal stress, the effects of different U concentrations on photosynthesis in 18-day-old Arabidopsis thaliana (Columbia ecotype) are investigated at two contrasting pH levels, pH 4.5 and pH 7.5. At pH 4.5, U is highly taken up by the roots but is poorly translocated to the shoots, while at pH 7.5, less U is taken up but the translocation is higher. The lower U concentrations in the shoots at pH 4.5 are accompanied by a more reduced leaf growth as compared to pH 7.5. In addition, U does not influence the photosynthetic machinery at pH 7.5, while an optimization of the photosynthesis takes place after U exposure at pH 4.5. As such, more of the absorbed quanta are effectively used for photosynthesis accompanied by a decreased non-photochemical quenching and an increased electron transport rate. Since the enhanced photosynthesis at pH 4.5 is accompanied by a decreased growth, we suggest that the energy produced during photosynthesis is used for defence reactions against U-induced oxidative stress rather than for growth. As such, a high discrepancy was observed between the two pH levels, with an optimized photosynthetic apparatus at pH 4.5 and almost no effects at pH 7.5.

Unexpected lack of deleterious effects of uranium on physiological systems following a chronic oral intake in adult rat.

Uranium level in drinking water is usually in the range of microgram-per-liter, but this value may be as much as 100 to 1000 times higher in some areas, which may raise question about the health consequences for human populations living in these areas. Our purpose was to improve knowledge of chemical effects of uranium following chronic ingestion. Experiments were performed on rats contaminated for 9 months via drinking water containing depleted uranium (0.2, 2, 5, 10, 20, 40, or 120 mg/L). Blood biochemical and hematological indicators were measured and several different types of investigations (molecular, functional, and structural) were conducted in organs (intestine, liver, kidneys, hematopoietic cells, and brain). The specific sensitivity of the organs to uranium was deduced from nondeleterious biological effects, with the following thresholds (in mg/L): 0.2 for brain, >2 for liver, >10 for kidneys, and >20 for intestine, indicating a NOAEL (No-Observed-Adverse-Effect Level) threshold for uranium superior to 120 m g/L. Based on the chemical uranium toxicity, the tolerable daily intake calculation yields a guideline value for humans of 1350 µg/L. This value was higher than the WHO value of 30 µg/L, indicating that this WHO guideline for uranium content in drinking water is very protective and might be reconsidered.