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.

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.

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.

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.

The impact of homologous recombination repair deficiency on depleted uranium clastogenicity in Chinese hamster ovary cells: XRCC3 protects cells from chromosome aberrations, but increases chromosome fragmentation.

Depleted uranium (DU) is extensively used in both industry and military applications. The potential for civilian and military personnel exposure to DU is rising, but there are limited data on the potential health hazards of DU exposure. Previous laboratory research indicates DU is a potential carcinogen, but epidemiological studies remain inconclusive. DU is genotoxic, inducing DNA double strand breaks, chromosome damage and mutations, but the mechanisms of genotoxicity or repair pathways involved in protecting cells against DU-induced damage remain unknown. The purpose of this study was to investigate the effects of homologous recombination repair deficiency on DU-induced genotoxicity using RAD51D and XRCC3-deficient Chinese hamster ovary (CHO) cell lines. Cells deficient in XRCC3 (irs1SF) exhibited similar cytotoxicity after DU exposure compared to wild-type (AA8) and XRCC3-complemented (1SFwt8) cells, but DU induced more break-type and fusion-type lesions in XRCC3-deficient cells compared to wild-type and XRCC3-complemented cells. Surprisingly, loss of RAD51D did not affect DU-induced cytotoxicity or genotoxicity. DU induced selective X-chromosome fragmentation irrespective of RAD51D status, but loss of XRCC3 nearly eliminated fragmentation observed after DU exposure in wild-type and XRCC3-complemented cells. Thus, XRCC3, but not RAD51D, protects cells from DU-induced breaks and fusions and also plays a role in DU-induced chromosome fragmentation.

Glutathione and transpiration as key factors conditioning oxidative stress in Arabidopsis thaliana exposed to uranium.

Although oxidative stress has been previously described in plants exposed to uranium (U), some uncertainty remains about the role of glutathione and tocopherol availability in the different responsiveness of plants to photo-oxidative damage. Moreover, in most cases, little consideration is given to the role of water transport in shoot heavy metal accumulation. Here, we investigated the effect of uranyl nitrate exposure (50 µM) on PSII and parameters involved in water transport (leaf transpiration and aquaporin gene expression) of Arabidopsis wild type (WT) and mutant plants that are deficient in tocopherol (vte1: null α/γ-tocopherol and vte4: null α-tocopherol) and glutathione biosynthesis (high content: cad1.3 and low content: cad2.1). We show how U exposure induced photosynthetic inhibition that entailed an electron sink/source imbalance that caused PSII photoinhibition in the mutants. The WT was the only line where U did not damage PSII. The increase in energy thermal dissipation observed in all the plants exposed to U did not avoid photo-oxidative damage of mutants. The maintenance of control of glutathione and malondialdehyde contents probed to be target points for the overcoming of photoinhibition in the WT. The relationship between leaf U content and leaf transpiration confirmed the relevance of water transport in heavy metals partitioning and accumulation in leaves, with the consequent implication of susceptibility to oxidative stress.

Effects of pH on uranium uptake and oxidative stress responses induced in Arabidopsis thaliana.

Uranium (U) causes oxidative stress in Arabidopsis thaliana plants grown at pH 5.5. However, U speciation and its toxicity strongly depend on environmental parameters, for example pH. It is unknown how different U species determine U uptake and translocation within plants and how they might affect the oxidative defense mechanisms of these plants. The present study analyzed U uptake and oxidative stress-related responses in A. thaliana (Columbia ecotype) under contrasted U chemical speciation conditions. The 18-d-old seedlings were exposed for 3 d to 25 µM U in a nutrient solution of which the pH was adjusted to 4.5, 5.5, 6.5, or 7.5. Results indicate that there is a different rate of U uptake and translocation at the different pHs, with high uptake and low translocation at low pH and lower uptake but higher translocation at high pH. After U exposure, an increased glutathione reductase activity and total glutathione concentration were observed in U-exposed roots, pointing toward an important role for glutathione in the root defense system against U either by chelation or by antioxidative defense mechanisms. In leaves, antioxidative defense mechanisms were activated on U exposure, indicated by increased superoxide dismutase and catalase activity. As it seems that U toxicity is influenced by pH, it is important to consider site-specific characteristics when making U risk assessments.

Uranium (U)-tolerant bacterial diversity from U ore deposit of Domiasiat in North-East India and its prospective utilisation in bioremediation.

Uranium (U)-tolerant aerobic chemo-heterotrophic bacteria were isolated from the sub-surface soils of U-rich deposits in Domiasiat, North East India. The bacterial community explored at molecular level by amplified ribosomal DNA restriction analysis (ARDRA) resulted in 51 distinct phylotypes. Bacterial community assemblages at the U mining site with the concentration of U ranging from 20 to 100 ppm, were found to be most diverse. Representative bacteria analysed by 16S rRNA gene sequencing were affiliated to Firmicutes (51%), Gammaproteobacteria (26%), Actinobacteria (11%), Bacteroidetes (10%) and Betaproteobacteria (2%). Representative strains removed more than 90% and 53% of U from 100 µM and 2 mM uranyl nitrate solutions, respectively, at pH 3.5 within 10 min of exposure and the activity was retained until 24 h. Overall, 76% of characterized isolates possessed phosphatase enzyme and 53% had PIB-type ATPase genes. This study generated baseline information on the diverse indigenous U-tolerant bacteria which could serve as an indicator to estimate the environmental impact expected to be caused by mining in the future. Also, these natural isolates efficient in uranium binding and harbouring phosphatase enzyme and metal-transporting genes could possibly play a vital role in the bioremediation of metal-/radionuclide-contaminated environments.

Synthesis, characterization and antibacterial activity of mixed ligand dioxouranium complexes of 8-hydroxyquinoline and some amino acids.

Mixed ligand complexes of dioxouranium(VI) of the type [UO2(Q)(L)-2H2O] have been synthesized using 8-hydroxyquinoline (HQ) as a primary ligand and N- and/or O- donor amino acids (HL) such as L-lysine, L-aspartic acid and L-cysteine as secondary ligands. The metal complexes have been characterized on the basis of elemental analysis, electrical conductance, room temperature magnetic susceptibility measurements, spectral and thermal studies. The electrical conductance studies of the complexes in DMF in 10(-3) M concentration indicate their non-electrolytic nature. Room temperature magnetic susceptibility measurements revealed diamagnetic nature of the complexes. Electronic absorption spectra of the complexes show intra-ligand and charge transfer transitions, respectively. Bonding of the metal ion through N- and O- donor atoms of the ligands is revealed by IR studies and the chemical environment of the protons is also confirmed by NMR studies. The thermal analysis data of the complexes indicate the presence of coordinated water molecules. The agar cup and tube dilution methods have been used to study the antibacterial activity of the complexes against the pathogenic bacteria S. aureus, C. diphtherinae, S. typhi and E. coli.

Modifications of the expression of genes involved in cerebral cholesterol metabolism in the rat following chronic ingestion of depleted uranium.

Depleted uranium results from the enrichment of natural uranium for energetic purpose. Its potential dispersion in the environment would set human populations at risk of being contaminated through ingestion. Uranium can build up in the brain and induce behavior disorders. As a major constituent of the myelin sheath, cholesterol is essential to brain function, and several neurological pathologies result from a disruption of cholesterol metabolism. To assess the effect of a chronic contamination with depleted uranium on cerebral cholesterol metabolism, rats were exposed to depleted uranium for 9 months through drinking water at 40 mg/l. The study focuses on gene expression. Cholesterol-catabolizing enzyme CYP46A1 displayed a 39% increase of its messenger RNA (mRNA) level. 3-Hydroxy-3-methylglutamyl CoA synthase gene expression rose from 91%. Concerning cholesterol transport, mRNA levels of scavenger receptor-B1 and adenosine triphosphate-binding cassette transporter A1 increased by 34% and that of apolipoprotein E by 75%. Concerning regulation, gene expression of nuclear receptors peroxisome proliferator-activated receptors alpha and gamma increased by 46% and 36% respectively, whereas that of retinoid-X-receptor decreased by 29%. In conclusion, a chronic internal contamination with depleted uranium does not affect the health status of rats but induces molecular changes in the dynamic equilibrium of the cerebral cholesterol pool.

Synthesis and biological activity of mixed ligand dioxouranium(VI) and thorium(IV) complexes.

Mixed ligand complexes of dioxouranium(VI) and thorium(IV) in the proportion 1:1:1 and 1:2:1 have been synthesized using 8-hydroxyquinoline as a primary ligand and L-proline and 4-hydroxy-L-proline as secondary ligands, respectively. The metal complexes have been characterized on the basis of elemental analysis, molar conductance, magnetic, spectral and thermal studies. The molar conductance studies of the complexes in DMF at 10(-3) M concentrations indicate their non-electrolytic nature. Room temperature magnetic susceptibility measurements revealed diamagnetic nature of the complexes. Electronic absorption spectra of the complexes show intra-ligand and charge transfer transitions, respectively. The thermal analysis data of the complexes indicates the presence of a coordinated water molecule/molecules. The tube dilution method has been used to study the antibacterial activity of the complexes against the pathogenic bacteria Staphylococcus aureus and Escherichia coli. The results have been compared against those of control tetracycline, which was screened simultaneously. The complexes have been screened for in vitro cytotoxicity (IC50) studies against Ehrlich ascites cells and Dalton's lymphoma ascites cells, respectively.

Isolation and characterization of four gram-positive nickel-tolerant microorganisms from contaminated sediments.

Microbial communities from riparian sediments contaminated with high levels of Ni and U were examined for metal-tolerant microorganisms. Isolation of four aerobic Ni-tolerant, Gram-positive heterotrophic bacteria indicated selection pressure from Ni. These isolates were identified as Arthrobacter oxydans NR-1, Streptomyces galbus NR-2, Streptomyces aureofaciens NR-3, and Kitasatospora cystarginea NR-4 based on partial 16S rDNA sequences. A functional gene microarray containing gene probes for functions associated with biogeochemical cycling, metal homeostasis, and organic contaminant degradation showed little overlap among the four isolates. Fifteen of the genes were detected in all four isolates with only two of these related to metal resistance, specifically to tellurium. Each of the four isolates also displayed resistance to at least one of six antibiotics tested, with resistance to kanamycin, gentamycin, and ciprofloxacin observed in at least two of the isolates. Further characterization of S. aureofaciens NR-3 and K. cystarginea NR-4 demonstrated that both isolates expressed Ni tolerance constitutively. In addition, both were able to grow in higher concentrations of Ni at pH 6 as compared with pH 7 (42.6 and 8.5 mM Ni at pH 6 and 7, respectively). Tolerance to Cd, Co, and Zn was also examined in these two isolates; a similar pH-dependent metal tolerance was observed when grown with Co and Zn. Neither isolate was tolerant to Cd. These findings suggest that Ni is exerting a selection pressure at this site for metal-resistant actinomycetes.

Kidney toxicity of ingested uranium from drinking water.

BACKGROUND: In experimental settings, uranium is toxic to kidneys, but effects on humans are unclear. Ingestion of water from drilled wells is a source of high uranium exposure in some populations. METHODS: Uranium exposure was measured in 95 men and 98 women aged 18 to 81 years who had used drinking water from drilled wells for an average of 16 years. Urinary N-acetyl-gamma-d-glucosaminidase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltransferase, and glutathione-S-transferase; serum cystatin C; and urinary and serum calcium, phosphate, glucose, and creatinine were measured to evaluate possible toxic effects of uranium on kidney cells and renal function. In addition, supine blood pressure was measured. Associations between uranium exposure and the outcome variables were modeled by using linear regression with adjustment for age, sex, body mass index, smoking, and analgesic use. RESULTS: Median uranium concentration in drinking water was 25 microg/L (interquartile range, 5 to 148 microg/L; maximum, 1,500 microg/L). Indicators of cytotoxicity and kidney function did not show evidence of renal damage. No statistically significant associations with uranium in urine, water, hair, or toenails was found for 10 kidney toxicity indicators. Uranium exposure was associated with greater diastolic and systolic blood pressures, and cumulative uranium intake was associated with increased glucose excretion in urine. CONCLUSION: Continuous uranium intake from drinking water, even at relatively high exposures, was not found to have cytotoxic effects on kidneys in humans.

Horizontal gene transfer of PIB-type ATPases among bacteria isolated from radionuclide- and metal-contaminated subsurface soils.

Aerobic heterotrophs were isolated from subsurface soil samples obtained from the U.S. Department of Energy's (DOE) Field Research Center (FRC) located at Oak Ridge, Tenn. The FRC represents a unique, extreme environment consisting of highly acidic soils with co-occurring heavy metals, radionuclides, and high nitrate concentrations. Four hundred isolates obtained from contaminated soil were assayed for heavy metal resistance, and a smaller subset was assayed for tolerance to uranium. The vast majority of the isolates were gram-positive bacteria and belonged to the high-G+C- and low-G+C-content genera Arthrobacter and Bacillus, respectively. Genomic DNA from a randomly chosen subset of 50 Pb-resistant (Pb(r)) isolates was amplified with PCR primers specific for P(IB)-type ATPases (i.e., pbrA/cadA/zntA). A total of 10 pbrA/cadA/zntA loci exhibited evidence of acquisition by horizontal gene transfer. A remarkable dissemination of the horizontally acquired P(IB)-type ATPases was supported by unusual DNA base compositions and phylogenetic incongruence. Numerous Pb(r) P(IB)-type ATPase-positive FRC isolates belonging to the genus Arthrobacter tolerated toxic concentrations of soluble U(VI) (UO(2)(2+)) at pH 4. These unrelated, yet synergistic, physiological traits observed in Arthrobacter isolates residing in the contaminated FRC subsurface may contribute to the survival of the organisms in such an extreme environment. This study is, to the best of our knowledge, the first study to report broad horizontal transfer of P(IB)-type ATPases in contaminated subsurface soils and is among the first studies to report uranium tolerance of aerobic heterotrophs obtained from the acidic subsurface at the DOE FRC.

Uranium induces TNF alpha secretion and MAPK activation in a rat alveolar macrophage cell line.

Uranium is a toxic heavy metal found mainly in the nuclear industry, but it is also used in the manufacturing of military munitions. Inhalation studies using animal models have demonstrated that long-term exposure to uranium can lead to the development of neoplasia and fibrosis at the pulmonary level. Because it has been demonstrated that such effects are often associated with inflammation, the effect of uranium on TNFalpha, IL-1beta, and IL-10 synthesis by macrophages was assessed in vitro using the NR8383 cell line. Our results show that a significant TNFalpha secretion was induced by uranium but not by other metals such as gadolinium. However, IL-1beta and IL-10 secretions were unaffected by uranium treatment. TNFalpha secretion was detectable since 50 microM of uranium and was maximal after 24 h of exposure. Determination of the mechanisms of uranium-induced TNFalpha production was assessed through the evaluation of protein kinases activation. Our results showed that uranium treatment induced c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) activation. The use of pharmacological inhibitors suggested that both p38 MAPK and protein kinase C (PKC) participate in the signal transduction of uranium-induced TNFalpha secretion. The regulation of TNFalpha secretion involves TNFalpha mRNA accumulation at least through the stabilization of TNFalpha mRNA, but p38 MAPK did not appear to be involved in this stabilization. However, this observation does not exclude regulation of TNFalpha synthesis at the transcriptional level, which remains to be demonstrated. Taking together, these results suggest that uranium can induce TNFalpha secretion by macrophages, thus contributing to a better understanding of the pathological effect of uranium on the lung.

Staining of intracellular deposits of uranium in cultured murine macrophages.

In our studies of the health effects of internalized depleted uranium, we developed a simple and rapid light microscopic method to stain specifically intracellular uranium deposits. Using J774 cells, a mouse macrophage line, treated with uranyl nitrate and the pyridylazo dye 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol, uranium uptake by the cells was followed. Specificity of the stain for uranium was accomplished by using masking agents to prevent the interaction of the stain with other metals. Prestaining wash consisting of a mixture of sodium citrate and ethylenediaminetetraacetic acid eliminated staining of metals other than uranium. The staining solution consisted of the pyridylazo dye in borate buffer along with a quaternary ammonium salt, ethylhexadecyldimethylammonium bromide, and the aforementioned sodium citrate/ethylenediaminetetraacetic acid mixture. The buffer was essential for maintaining the pH within the optimum range of 8 to 12, and the quaternary ammonium salt prevented precipitation of the dye. Staining was conducted at room temperature and was complete in 30 min. Staining intensity correlated with both uranyl nitrate concentration and incubation time. Our method provides a simple procedure for detecting intracellular uranium deposits in macrophages.

Ca(2+)-blockable, poorly selective cation channels in the apical membrane of amphibian epithelia. Tetracaine blocks the UO2(2+)-insensitive pathway.

We examined the effect of the local anesthetic tetracaine on the Ca(2+)-blockable, poorly selective cation channels in the isolated skin of Rana temporaria and the urinary bladder of Bufo marinus using noise analysis and microelectrode impalements. Experiments with frog skin demonstrated that mucosal concentrations of the compound up to 100 microM did not affect the Na+ current through type S channels (slowly fluctuating, UO2(2+)-blockable channels) and the associated noise. On the other hand, 20 microM mucosal tetracaine already suffices to inhibit approximately 50% of the current carried by Cs+ and Na+ through channel type F (fast fluctuating, UO2(2+)-insensitive channel) and So of the associated Lorentzian component. With 100 microM of the inhibitor the current and So values were reduced by at least 70-80%. The time course of the response to serosal tetracaine was markedly slower and the effects on the current and So were smaller. Possible effects on the basolateral K+ conductance were excluded on the basis of the lack of response of transepithelial K+ movements to 100 microM tetracaine. UO2(2+) and tetracaine together blocked the poorly selective cation pathways almost completely. Moreover, both agents retain their inhibitory effect in the presence of the other. In toad urinary bladder, the Ca(2+)-blockable channel is also tetracaine blockable. The concentration required for half-maximal inhibition is approximately 100 microM in SO4(2-) and approximately 20 microM in Cl-. The data with tetracaine complement those obtained with UO2(2+) and support the idea that the Ca(2+)-blockable current proceeds through two distinct classes of cation channels. Using tetracaine and UO2(2+) as channel-specific compounds, we demonstrated with microelectrode measurements that both channel types are located in the granulosum cells.

[Changes in cellular radiosensitivity by modifying the cytoplasmic membranes]. / Izmenenie radiochuvstvitel'nosti kletok putem modifikatsii tsitoplazmaticheskikh membran.

The radiosensitivity of mouse myeloma and E. coli cells in the presence of Mg2+ and UO2(2+) ions has been investigated. It has been shown that Mg2+ ions (10(-4) M) do not influence the viability of E. coli and mouse myeloma cells. The presence of Mg2+ ions during irradiation reduces the survival rate of E. coli cells, but the addition of Mg2+ ions after irradiation does not influence the radiosensitivity of E. coli cells. Comparison of the results on the influence of Mg2+ ions upon cells and bilayer lipid membranes (BLM) permits us to suppose that Mg2+ ions increase the positive charge of the membranes thus promoting the increase in the number of short-lived radiolysis products which impair membranes and increase cell radiosensitivity. UO2(2+) ions (10(-4) M) increase the radioresistance of E. coli cells which can be associated with the increase in the lateral membrane viscosity, as it was shown in the studies on BLM.

Relationship between kidney burden and radiation dose from chronic ingestion of U: implications for radiation standards for the public.

Metabolic models for U in adults recommended by Wrenn et al. (1985) and the International Commission on Radiological Protection (ICRP 1979a) were used to study the relationship between kidney burden and radiation dose from chronic ingestion of soluble 238U or natural U and whether current radiation standards for the public provide adequate protection against chemical toxicity from U in the kidney. We assumed that the threshold concentration for chemical toxicity is 1 microgram of U g-1 of kidney and that a safety factor of 10 should be applied in limiting kidney burdens for maximally exposed individuals in the general public. We found that a limit on annual effective dose equivalent of 1 mSv (0.1 rem) for chronic exposures of the public from all sources, as recommended by the ICRP (1985) and the National Council on Radiation Protection and Measurements (NCRP 1987), corresponds to concentrations of U in the kidney from chronic ingestion that exceed the assumed threshold for chemical toxicity of 1 microgram g-1 only for 238U using the metabolic model of the ICRP (1979a). However, using either metabolic model (ICRP 1979a; Wrenn et al. 1985), the predicted concentrations of U in the kidney exceeded the limit of 0.1 microgram g-1, based on the assumed safety factor for protection of the public, for both 238U and natural U. From these results, we concluded that chemical toxicity should be considered in developing health protection standards for the public for ingestion of soluble 238U or natural U. Environmental radiation standards for certain practices established by the U.S. Environmental Protection Agency and Nuclear Regulatory Commission (EPA 1987a, 1987b, 1987c, 1987d; NRC 1988a) are consistent with a limit on annual effective dose equivalent of 0.25 mSv (25 mrem) per practice. If the metabolic model of Wrenn et al. (1985) is assumed to be appropriate for chronic ingestion of soluble U in the environment, then the dose limit of 0.25 mSv corresponds to a concentration of 238U or natural U in the kidney that is below the assumed limit of 0.1 microgram g-1 for members of the public. Inhalation of soluble and insoluble U and ingestion of insoluble U were considered. Except for inhalation of soluble U, these modes of intake reduced predicted concentrations in the kidney per unit effective dose equivalent compared with values for ingestion of soluble U. Unresolved issues of importance for determining the significance of chemical toxicity relative to radiation dose in establishing limits on public exposures for U also are discussed.