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PubMed2005

Uranyl acetate induces hprt mutations and uranium-DNA adducts in Chinese hamster ovary EM9 cells.

Questions about possible adverse health effects from exposures to uranium have arisen as a result of uranium mining, residual mine tailings and use of depleted uranium in the military. The purpose of the current study was to measure the toxicity of depleted uranium as uranyl acetate (UA) in mammalian cells. The activity of UA in the parental CHO AA8 line was compared with that in the XRCC1-deficient CHO EM9 line. Cytotoxicity was measured by clonogenic survival. A dose of 200 microM UA over 24 h produced 3.1-fold greater cell death in the CHO EM9 than the CHO AA8 line, and a dose of 300 microM was 1.7-fold more cytotoxic. Mutagenicity at the hypoxanthine (guanine) phosphoribosyltransferase (hprt) locus was measured by selection with 6-thioguanine. A dose of 200 microM UA produced approximately 5-fold higher averaged induced mutant frequency in the CHO EM9 line relative to the CHO AA8 line. The generation of DNA strand breaks was measured by the alkaline comet assay at 40 min and 24 h exposures. DNA strand breaks were detected in both lines; however a dose response may have been masked by U-DNA adducts or crosslinks. Uranium-DNA adducts were measured by inductively coupled plasma optical emission spectroscopy (ICP-OES) at 24 and 48 h exposures. A maximum adduct level of 8 U atoms/10(3) DNA-P for the 300 microM dose was found in the EM9 line after 48 h. This is the first report of the formation of uranium-DNA adducts and mutations in mammalian cells after direct exposure to a depleted uranium compound. Data suggest that uranium could be chemically genotoxic and mutagenic through the formation of strand breaks and covalent U-DNA adducts. Thus the health risks for uranium exposure could go beyond those for radiation exposure.

Animals↗
PubMed1999

Empirical Identification of Uranium Oxides and Fluorides Using Electron Energy-loss Spectroscopy in the Transmission Electron Microscope.

: A set of uranium compound particles relevant to contaminated soils and other environmental concerns surrounding uranium bioavailability were studied by electron energy-loss spectroscopy (EELS). Core-loss EELS results suggest that uranium 4(+) compounds have an energy loss resolvable from 6(+) compounds. Shoulders on the uranium O(4,5) edge further distinguish UO(2) from UF(4). Low-loss characteristics distinguish carbon-free uranium oxide specimens on holey substrates. In the presence of carbon, correction techniques must be applied. Uranium oxides, fluorides, and minerals show a tendency toward reduction of uranium toward 4(+) under the beam. The electron dose required to achieve the transformation from 6(+) to 4(+) is more severe than that usually required to obtain satisfactory spectra, but the possibility for reduction should be considered. The conditions for low-loss analysis need not be as vigorous as those for core losses, and can be done without altering the valence of most oxides.

Journal Article↗
PubMed2003

Sensitivity of a low energy Ge detector system for in vivo monitoring in the framework of ICRP 78 applications.

In in vivo detection of internal contamination by actinides the minimum detectable activities (MDAs) correspond to significant doses, so the sensitivity of the detection system is the key to establishing adequate individual monitoring programmes for internal exposure to these radionuclides. The whole body counting (WBC) faculty at CIEMAT uses a low-energy Ge detector system with different available counting geometries to estimate the retention of actinides in the lungs and evaluate 125I in thyroid and 241Am in bone (skull and knee). A study of the factors and uncertainties involved in estimations of MDA is presented for lung and thyroid monitoring. The dependence of detection limits on counting efficiency in the measurement of low-energy emitters in the lungs has been carefully studied, carrying out a comparison among different biometric equations obtained by ultrasound techniques for estimations of chest wall thickness. Dosimetric implications of the estimated MDAs are taken into account in the framework of ICRP 78 application and considering Spanish regulations. The main interest in lung measurements is for the assessment of occupational exposure. This work confirms the low-energy Ge detector system to be an adequate in vivo technique for the routine monitoring of internal exposure to most insoluble uranium compounds (detection of 3% enriched uranium in lungs), and also to be useful in special monitoring programmes or in the case of incidents when the detection of 241Am is required.

Actinoid Series Elements↗
PubMed1999

The effects of the initial lung deposit on uranium biokinetics after administration as UF4 and UO4.

This study was designed to assess the effect of the initial lung deposit (ILD) on uranium biokinetics in rats after intracheal instillation of biologically soluble uranium compounds. Rats received various doses of either UO4 or UF4 dust. The uranium content was determined in the kidneys, lungs, remaining carcass, urine and faeces at intervals of up to 30 days. The percentages of uranium absorbed into blood, transferred to tissues, and excreted in urine were independent of the uranium lung deposit for the two compounds. The K/K + U ratio 24 h after installation (K is the per cent of uranium retained in the kidneys and U the per cent excreted in urine) which can be used to evaluate kidney function, was essentially constant in the range from 0.02 to 12.5 microg U g(-1) kidneys.

Animals↗
PubMed2001

Hartree-Fock study of orbital magnetic moments in 3d and 5f magnets and X-ray magnetic circular dichroism.

The spin (Ms) and orbital magnetic moments (Mo) of the uranium 5f state in the ferromagnetic compound uranium sulfide (US) and of the cobalt 3d state in various transition-metal superlattices are calculated on the basis of a tight-binding model, in which the intra-atomic f-f or d-d multipole interaction is taken into account using the Hartree-Fock (HF) approximation. The parameters in the model are determined on the basis of available first-principles calculations. For US, the calculated ratio Mo/Ms and magnetic circular dichroism spectrum for U M4,5 absorption are in good agreement with the experimental results. Inclusion of the expectation values of the spin-off-diagonal operators in addition to the number operators in the 5f state is found to be crucially important when describing the 5f magnetic state. A difference in enhancement of Mo of the Co atom between the Co/Pd and Co/Cu superlattices is discussed on the basis of a semi-quantitative calculation, assuming ferromagnetism.

Journal Article↗
PubMed1999

Influence of uranium(VI) speciation for the evaluation of in vitro uranium cytotoxicity on LLC-PK1 cells.

Very few data are available concerning the in vitro toxicity of uranium. In this work, we have determined the experimental chemical conditions permitting the observation of uranium(VI) cytotoxicity on LLC-PK1 cells. Uranium solutions made either by dissolving uranyl acetate or nitrate crystals, or by complexing uranium with bicarbonate, phosphate or citrate ligands, were prepared and tested. Experiments demonstrated that only uranium solutions containing citrate and bicarbonate ligands concentrations tenfold higher than the metal, were soluble in the cell culture medium. Cytotoxicity studies of all these uranium compounds were performed on LLC-PK1 cells and compared using LDH release, neutral red uptake and MTT assays. Dose dependent cytotoxicity curves were only obtained with uranium-bicarbonate medium. This study has revealed a toxicity of uranium-bicarbonate complexes for 24 h expositions and for concentrations ranging from 7 x 10(-4)-10(-3) M, under these conditions, the CI50 (cytotoxicity index) was evaluated between 8.5 and 9 x 10(-4) M. In contrast, we noticed a lack of cytotoxicity response for uranium(VI)-citrate complexes. Electron transmission microscopy studies revealed, when LLC-PK1 cells were exposed to the uranium-bicarbonate system, that uranium penetrated and precipitated within the cytoplasmic compartment. Morphological studies conducted with citrate complexes did not show any cellular intake of uranium.

Animals↗
PubMed2001

Reduction of uranium transfer by local chelation in simulated wounds in rats.

The aim of the paper is to develop a new approach to treat uranium-contaminated wounds. The efficacy of a local uranium chelator, carballylic amido bis phosphonic acid (CAPBP) was assessed using two different uranium compounds. Rats were contaminated by intramuscular injections of uranyl nitrate or an industrial U04 compound to simulate wound contamination. CAPBP was injected intramuscularly (i.m.) or intraperitoneally (i.p.) at a dosage of 30 micromol kg(-1). In one experiment, the local administration of CAPBP was combined with a systemic administration of ethane-1-hydroxy-1,1-biphosphonate (EHBP). The local CAPBP treatment resulted in increased retention of uranium at the wound site: about 30% for uranyl nitrate or U04 after the first day and about 15% of UO4 after the third day. Consequently, it reduced uranium translocation into the blood and deposition in the kidneys and bone. The combined treatment reduced the uranium deposits in the kidneys, bone and carcass to about one-half of those observed in controls 3 days after U04 contamination. The local CAPBP treatment increased the interval of time between contamination and uranium deposit in the target organs. Thus, it can increase the efficacy of nonspecific local treatments or specific systemic treatments. It could be given rapidly through spray or gel after an accident.

Animals↗
PubMed1996

Role of alveolar macrophages in the dissolution of two different industrial uranium oxides.

This study was aimed at assessing and understanding some mechanisms involved in the intracellular particle transformation of two uranium oxides (U3O8 and UO2 + Umetal) produced by a new isotopic enrichment plant using laser technology. Instillations were conducted on rats with both uranium compounds and alveolar macrophages were harvested at different dates and prepared in order to be studied using transmission electron microscopy and electron energy loss spectrometry (EELS). The presence of particles in the cells was observed from the first day after instillation, and crystalline needles of uranyl phosphate appeared in the cytoplasm of the cells. These needles were more numerous after instillation with the mixture UO2 + Umetal than after administration of U3O8 and may be correlated with the higher solubility of UO2 + Umetal observed in vitro. The formation of insoluble needles in lysosomes is consistent with the insolubilisation of uranium observed after phagocytosis by alveolar macrophages.

Air Pollutants, Occupational↗
PubMed1985

Metabolism of an industrial uranium trioxide dust after deposition in the rat lung.

UNLABELLED: Uranium trioxide, produced industrially, was administered to rats either by inhalation or direct injection of an aqueous suspension into the lungs. THE RESULTS: show that uranium was cleared rapidly from the lungs, mainly to the blood; show that distribution of uranium among body tissues, and the fraction of the systemic content excreted in urine, was similar to that obtained for other transportable hexavalent uranium compounds; suggest that urine monitoring data would be of more value than lung radioactivity counting measurements for assessing occupational human exposure; indicate that for setting exposure limits by inhalation the uranium trioxide should be considered a highly transportable compound. Thus intakes by workers should be restricted to those recommended for short-term exposures and not those based on an annual limit.

Aerosols↗
PubMed1996

Overview of the Fernald Dosimetry Reconstruction Project and source term estimates for 1951-1988.

The Feed Materials Production Center, northwest of Cincinnati, processed uranium concentrates and uranium compounds recycled from other stages of nuclear weapons production, as well as some uranium ore and thorium. Particulate releases were primarily uranium (natural, depleted, and slightly enriched. In addition, two large silos containing radium-bearing residues were emission sources of radon and its decay products. The Fernald Dosimetry Reconstruction Project was undertaken to help the Centers for Disease Control and Prevention to evaluate the impact of the Feed Materials Production Center on the public from radionuclides released to the environment from 1951 through 1988. At this point in the study, the project has estimated the quantities of radioactive materials released to air, surface water, and in groundwater; developed the methodology to describe the environmental transport of the materials; developed mathematical models to calculate the resulting radiation doses; and evaluated environmental monitoring data to verify that the estimates of releases and transport are reasonable. Thorough review of historical records and extensive interaction with former and current employees and residents have been the foundation for reconstructing routine operations, documenting accidents, and evaluating unmonitored emission sources. The largest releases of uranium to air and water occurred in the 1950's and 1960's. Radon releases from the silos remained elevated through most of the 1970's. The quantity of uranium released to surface water was much less than that released to air. Best estimates of releases are reported as median values, with associated uncertainties calculated as an integral part of the estimates. Screening calculations showed that atmospheric pathways dominate the total dose from Feed Materials Production Center releases. Accordingly, the local meteorology, effluent particle size and chemical form, and wet and dry deposition, were particularly important in this study. The final goal of the project is the calculation of radiation doses to people living in the study domain, which is represented by a circle with radius of 10 km centered on the Feed Materials Production Center production area.

Air Pollutants, Radioactive↗
PubMed1980

[Distribution of uranium in dental porcelains by means of the fission track method (author's transl)].

Porcelain teeth, some of which contain uranium compounds for aesthetic purpose, have been widely used in dental clinics. Hazardous effects due to uranium radiation have been suggested by recent publications. In the previous study, the authors reported the uranium content of porcelain teeth and radiation dose by it. In this study, using the fission track method, the authors examined spatial distribution of uranium in dental porcelain teeth (4 brands) which were marketed in Japan. From each sample of porcelain tooth, a 1-mm-thick specimen was sliced, and uranium content was measured at every 0.19 mm from labial side to lingual side for making a uranium distribution chart. Higher uranium concentration was found in Trubyte Bioblend porcelain teeth (USA) and they showed almost uniform distribution of uranium, while those of the Japanese three brands indicated, in most case, comparatively lower concentration and found to be non-uniform distributions. Range of uranium concentration in these brands were N.D. approximately 5.2 ppm (Shofu-Ace), N.D. approximately 342 ppm (Shofu-Real), N.D. approximately 47 ppm (G.C. Livdent) and N.D. approximately 235 ppm (Trubyte Bioblend), respectively.

Dental Porcelain↗
PubMed1985

Alveolar wound healing alteration under uranyl nitrate intoxication.

The deposit of uranium compounds in calcifying zones has been demonstrated in bone. Nevertheless, no studies on the effect of uranium on osteogenesis have been performed. A histologic and histometric study of the effect of a single intraperitoneal injection of 2 mg/kg of body weight of uranyl nitrate on bone formation is presented. It was performed on rats' healing sockets, 14 days after tooth extraction. The alveolar bone volume (15 X 10(5) micron vs. 34 X 10(5) micron2), total bone formation areas (4.85% vs. 19.55%), and volume density of bone in the alveolar apical third (0.26 vs. 0.40) were significantly lower in intoxicated animals than in the controls. These results indicate the inhibitory effect of uranyl nitrate on bone formation.

Alveolar Process↗
PubMed1986

An assay for ribonuclease activity, based on ultraviolet absorption of RNA hydrolysate, using phosphotungstic acid.

In the method for the determination of ribonuclease activity that depends on the ultraviolet absorption of the RNA hydrolysate, the uranium reagent (25% perchloric acid solution containing 0.75% uranyl acetate) is commonly used for the efficient precipitation of the unhydrolyzed RNA. However, this reagent is always contaminated by the presence of radioactive isotopes. Radioactive uranium is one of the substances used for atomic nuclear fuel and therefore, at least in Japan, the use of uranium compounds requires permission from the government. We tried to find another efficient and non-radioactive precipitant of RNA to replace the uranium reagent, and have developed a phosphotungsten reagent (25% perchloric acid solution containing 0.75% phosphotungstic acid plus 0.6% bovine serum albumin solution) which functions as efficiently as the uranium reagent in the precipitation of RNA. A cell-free crude extract of Dictyostelium discoideum was used as the source of ribonuclease.

Chemical Precipitation↗
PubMedDate not supplied

Use of urease-bromothymol blue-agar method for large-scale testing of urine on grain and seeds.

The current AOAC method (963.28) for large-scale (50 g) testing of urine on grain is based on the reaction of sodium in urine with magnesium uranyl acetate. Detection of sodium suggests that urine is present and that a test for urea is appropriate. Urea is detected with urease-bromothymol blue-paper and is confirmed through its reaction with xanthydrol to form dixanthylurea crystals, which are detected microscopically. The initial nonspecific test for sodium can be influenced by the presence of salt or other sodium compounds. Furthermore, the magnesium uranyl acetate spray used in Method 963.28 potentially exposes the analyst to the aerosol of a volatile, toxic uranium compound. Excess reagents and analyzed test portions must be disposed of as radioactive waste. In addition, Method 963.28 requires several steps to determine the presence of urea. The alternative AOAC method (972.41) tests for the presence of urea from urine on individual seeds. Urea is enzymatically decomposed to ammonia and carbon dioxide by urease. Liberated ammonia shifts the pH, changing the color of the indicator in the agar from yellow to blue. This study adapts Method 972.41 to larger test samples. Up to 25 g grains and seeds are sprayed with urease test agar instead of being individually immersed in the urease test agar. The modified method was used to analyze urea on seeds and grains of 24 plants from 4 families. The method has a limit of detection of one seed contaminated with 1 microgram urea.

Aerosols↗
PubMed1985

Renal toxicity in uranium mill workers.

Although the kidney is the critical organ limiting occupational exposure to soluble uranium compounds, there have been no adequate studies evaluating renal tubular dysfunction in chronically exposed workers. The present investigation evaluated kidney function among 39 uranium mill workers and 36 local cement plant workers of equivalent age, sex, and race. The uranium workers showed a significantly higher excretion of beta-2-microglobulin and five amino acids than the reference group. Although the levels of tubular proteinuria were mild, a dose-effect relation existed between the clearance of beta-2-microglobulin, relative to that of creatinine, and the length of time that the uranium workers had spent in the yellowcake drying and packaging area, the work area with the highest exposures to soluble uranium. Age did not account for this relationship. Glomerular function was significantly better among the uranium workers than among the referents, though this may have been the result of differences in the physical activity of the groups during the collection period. The data presented suggest reduced renal proximal tubular reabsorbtion of amino acids and of low molecular weight proteins, consistent with uranium nephrotoxicity.

Adult↗