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Divalent Metal Transporter 1 (DMT1) is a transmembrane transporter located at the apical membrane of enterocytes and implicated in the duodenal uptake of iron. Results from expression experiments in Xenopus oocytes indicate that DMT1 can mediate transport of a wide range of divalent metals other than iron. The aim of the present study was to examine the effect of iron treatment on the uptake and transepithelial movement of 63Ni and to correlate that to DMT1 messenger RNA (mRNA) levels in human intestinal Caco-2 cells. Twenty-one days after confluent Caco-2 cell monolayers were treated for 1 or 3 days with medium supplemented with Fe(NTA)2 or control medium and 63Ni transport and DMT1 gene expression were measured at both time points. Functional effects of the iron treatment were assessed by examining uptake and transepithelial movement of 59Fe. Iron treatment resulted in decreased DMT1 gene expression which correlated well with the uptake of 59Fe and 63Ni into fully differentiated Caco-2 cells. This indicates that DMT1 is responsible for the apical transport of these metals in the intestinal epithelium and suggests that adequate iron intake and status will limit nickel absorption.

Porous titanium-nickel (PTN) devices represent an alternative to traditional cage implants. PTN materials possess an interconnecting network of pores with capillarity properties that may promote bone ingrowth, long-term fixation, and intervertebral fusion without the need for bone grafting. However, their considerable surface area and nickel content may elicit concerns over sensitization potential. Therefore, PTN surface corrosion and nickel release resistance must be carefully studied. To evaluate this possibility, a PTN interbody fusion device (IFD) was compared to a conventional nonporous cage made of TiAlV, a well-known biocompatible biomaterial, in a sheep model. PTN and TiAlV IFDs were inserted at two non-contiguous lumbar sites for 3, 6, and 12 months postsurgery. Their surface was then evaluated by scanning electron microscopy (SEM) combined with backscattered electron analysis (BSE). No evidence of surface corrosion was observed either pre- or postimplantation, regardless of device type. Dosage of nickel ions was also performed with the use of inductively coupled plasma-mass spectrometry (ICP-MS). Blood nickel levels were observed to be within acceptable levels at all postinstrumentation times. Nickel content in PTN-adjacent tissue, as well as in detoxification and remote organs, was equivalent both in PTN-treated and control sheep. Therefore, porous titanium-nickel demonstrated resistance to both in vivo surface corrosion and nickel ion release and compared very well with a conventional titanium implant in the course of a 12-month sheep study., ((c) 2003 Wiley Periodicals, Inc.)

Biosorption of metal ions with Penicillium chrysogenum mycelium is described in this article. Alkaline pretreatment was used to remove proteins and nucleic acids from cells, and this treatment increased the adsorption capacities, for Cr3+ from 18.6 mg g(-1) to 27.2 mg g(-1), for Ni2+ from 13.2 mg g(-1) to 19.2 mg g(-1), for Zn2+ from 6.8 mg g(-1) to 24.5 mg g(-1). The adsorption of metal ions was strongly pH dependent. The mycelium could be used for large-scale removal of Cr3+ from tannery wastewater. The results show that this inexpensive mycelium adsorbent has potential in industry because of its high adsorption capacity. The main chelating sites are amino groups (-NH2) of chitosan in the mycelium. A new model is established, which describes the relation of adsorption of metal ions on pH according to amino group chelating with metal ions and H+. The relative errors of simulation for Cu2+, Ni2+, Zn2+, and Cr3+ are 4.66%, 5.45%,11.55%, and 1.69%, respectively.

Aims: The aim was to develop a new, efficient and cost-effective biosorbent for the removal of heavy metals from aqueous solution., Methods and Results: A new biosorbent was developed by immobilizing a unicellular green microalga Chlorella sorokiniana within luffa sponge discs and used for the removal of metal ions from aqueous solution. Microalgal-luffa sponge immobilized discs (MLIDs) removed Ni(II) very rapidly, with 97% of equilibrium loading being reached in 5 min. MLIDs were tested for their potential to remove Ni(II) from aqueous solution in fixed-bed column bioreactor. The regenerated MLIDs retained 92.9% of the initial binding capacity for Ni(II) up to five cycles of reuse., Conclusions: In this study for the first time, C. sorokiniana biomass immobilized within luffa sponge disc was successfully used as a metal biosorbent for the removal of Ni(II). It appears that MLIDs can be used as an effective biosorbent for efficient removal of Ni(II) or other metals from aqueous solution., Significance and Impact of the Study: MLIDs biosorption system was shown to have good biosorption properties with respect to Ni(II). Efficient metal removal ability of MLIDs, low cost and simplicity of the technique used for the preparation of MILDs could provide an attractive strategy for developing high-affinity biosorption system for heavy metal removal.

Elemental composition of soil, herbaceous and woody plant species, and the muscle and liver tissue of two common small mammal species were determined in a wetland ecosystem contaminated with Ni and U from nuclear target processing activities at the Savannah River Site, Aiken, SC. Species studied were black willow ( Salix nigra L.), rushes ( Juncus effusus L.), marsh rice rat ( Oryzomys palustris), and cotton rat ( Sigmodon hispidus). Two mature trees were sampled around the perimeter of the former de facto settling basin, and transect lines sampling rushes and trapping small mammals were laid across the wetland area, close to a wooden spillway that previously enclosed the pond. Ni and U concentrations were elevated to contaminant levels; with a total concentration of 1,065 (+/- 54) mg kg(-1) U and 526.7 (+/-18.3) mg kg(-1) Ni within the soil. Transfer of contaminants into woody and herbaceous plant tissues was higher for Ni than for U, which appeared to remain bound to the outside of root tissues, with very little (0.03 +/- 0.001 mg kg(-1)) U detectable within the leaf tissues. This indicated a lower bioavailability of U than the cocontaminant Ni. Trees sampled from the drier margins of the pond area contained more Ni within their leaf tissues than the rushes sampled from the wetter floodplain area, with leaf tissues concentrations of Ni of approximately 75.5 (+/- 3.6) mg kg(-1) Ni. Ni concentrations were also elevated in small mammal tissues. Transfer factors of contaminants indicated that U bioavailability is negligable in this wetland ecosystem.

In vivo and in vitro studies have shown for the first time that nickel binds maximally to RNA as compared to DNA. The distribution of radiolabeled nickel in various subcellular fractions of liver, kidney, spleen, and lungs of rats has shown that it was mostly localized in the nuclear fraction of each organ, where it was bound to RNA and not to DNA or to proteins. Significant differences between infrared (IR) spectra of RNA and RNA incubated with nickel chloride further corroborate these findings. Parallel experiments with DNA did not show any such effects. Nickel may, therefore, be acting as a carcinogen by controlling gene expression post-transcriptionally.

Growing concern about heavy metal contamination of agricultural lands under long-term application of inorganic fertilizers and organic wastes makes periodic risk assessment of heavy metal accumulation in arable lands imperative. As a part of a much larger study to systematically document the status of heavy metals in savanna soils this study investigated the distribution and dynamics of Cr and Ni in a savanna soil after 50 years of continuous cultivation and application of inorganic fertilizers and organic manures. The cultivated fields were fertilized with inorganic fertilizers (NPK), farmyard manure (FYM), FYM+NPK for 50 years and a control plot under continuous cultivation for 50 years but did not receive either FYM or NPK. Two uncultivated or natural sites were sampled as reference conditions for assessing the dynamics of Cr and Ni induced by cultivation and management practices. The distribution of Cr and Ni in the soil profiles exhibited eluvial-illuvial patterns. Sand and clay fractions explained between 62 and 90% of the variance in Cr and Ni concentration and distribution in the soil profiles. Mean Cr concentrations ranged from 17 to 59 mg kg(-1), while Ni varied from <1 mg kg(-1) in the topsoil to 16 mg kg(-1) in the subsoil. Mass balance calculations showed a loss of 10% Cr and 17% Ni in the FYM field, and approximately 4% Cr and 11% Ni in the NPK field compared to the natural site after 50 years of cultivation. The control and FYM + NPK field had, however, a positive balance of Cr and Ni. In general, it was concluded that existing soil management practices in this region are unlikely to lead to Cr and Ni build-up probably because of low rates of application of inorganic fertilizers, farmyard manure and other organic wastes to the soils.

The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear because of limitations of the exposure data, inconsistent results across cohorts, and the presence of mixed exposures to water-insoluble nickel compounds and other confounders that are known or suspected carcinogens. Moreover, well-conducted animal inhalation studies, where exposures were solely to soluble nickel, failed to demonstrate a carcinogenic potential. Similar negative results were seen in animal oral studies. A model exists that relates respiratory carcinogenic potential to the bioavailability of nickel ion at nuclear sites within respiratory target cells. This model helps reconcile human, animal, and mechanistic data for soluble nickel compounds. For inhalation exposures, the predicted lack of bioavailability of nickel ion at target sites suggests that water-soluble nickel compounds, by themselves, will not be complete human carcinogens. However, if inhaled at concentrations high enough to induce chronic lung inflammation, these compounds may enhance carcinogenic risks associated with inhalation exposure to other substances. Overall, the weight of evidence indicates that inhalation exposure to soluble nickel alone will not cause cancer; moreover, if exposures are kept below levels that cause chronic respiratory toxicity, any possible tumor-enhancing effects (particularly in smokers) would be avoided.

Ni(II) compounds are well known as human carcinogens, though the molecular events which are responsible for this are not yet fully understood. It has been proposed that the binding of N(II) ions within the cell nucleus is a crucial element in the mechanism of carcinogenesis. The most abundant proteins in the cell nucleus are histones, and this makes them the prime candidates for this role. This article is a review of our recent studies of histone H4 models of Ni(II) binding. We analyzed the sequence of the N-terminal tail of the histone H4, Ac-SGRGKGGKGLGKGGAKRH(18)RKVL-Am, for Ni(II) binding. This site has been proposed mainly because of the potent inhibitory effect of Ni(II) on the acetylation of lysine residues near the histidine H(18), and also because of the accessibility of the H4 tail in the histone octamer. Combined potentiometric and spectroscopic studies showed that the histidine 18 acted as an anchoring binding site for metal ions in the peptide investigated. Comparison with the results for Cu(II) binding are also reported. The results allowed us to propose that the binding of Ni(II) is able to promote a secondary structure with organized side-chain orientation on the N-terminal tail of histone H4.

Benthic-feeding fish residing in Ni-contaminated systems are exposed to Ni through ingestion of contaminated food items and sediments. Lake whitefish (Coregonus clupeaformis) were fed diets at a ration of 0.5% of body weight three times a week containing 0, 10, 100, and 1000 microg Ni/g (as NiSO(4)) for 10, 31, and 104 days. Stomach, pyloric caeca, intestine, kidney, liver, gall bladder, gonad, gill, bone, muscle, skin, and scales were analyzed to evaluate the accumulation and distribution of Ni. Fish fed the medium and high dose diets accumulated significant amounts of Ni in a majority of the tissues sampled, even after only 10 days of exposure. Ni concentrations were highest in intestine and pyloric caeca of whitefish fed 1000 microg Ni/g on day 10, but decreased on subsequent sampling days, possibly due to protective mechanisms. Ni accumulation in stomach, kidney, liver, gill, skin, and scales was dose and duration-dependent. Ni concentrations measured in bone, gall bladder, gonad, and muscle of fish fed the control diet for 10 days and fish fed the high dose diet for all durations appeared to increase in a duration-dependent manner. Exposure to Ni altered the concentrations of Cu and Zn in tissues of lake whitefish. However, Cu and Zn concentrations in the tissues analyzed were variable and did not follow a common pattern or trend. The tissues that best assess dietary Ni bioavailability are kidney and scales. The toxicology of Ni in these fish is described in the next manuscript (Aquat. Toxicol., in press (b)).

The sublethal toxicity associated with exposure of adult lake whitefish (Coregonus clupeaformis) to diets containing 0, 10, 100, and 1000 microg Ni per g for 10, 31, and 104 days was assessed through the measurement of responses, through a range of levels of biological organization. The accumulation and distribution of Ni in these fish are described in the previous manuscript (Ptashynski and Klaverkamp, 2001. Aquat. Toxicol. in press). Hematological parameters, including concentrations of glucose and hemoglobin and hematocrit, were not different between control and treated fish. Organ and whole organism parameters, including LSI, growth, and condition factor, were also unaffected. Histopathological lesions in kidney and liver proved to be the most sensitive and reliable indicators of Ni exposure. In livers of treated fish, areas of focal necrosis and altered bile ducts were observed. Histological alterations were observed throughout the posterior kidneys, in glomeruli, tubules, collecting ducts, and hematopoietic tissue, in fish fed medium and high dose diets. In whitefish kidneys, the frequency (%) of altered distal tubules and fields of views with alterations increased with the dose and duration of exposure. Significant increases in metallothionein concentrations were observed in intestine of whitefish fed the high dose diet on day 10, but these increases were not sustained. Significant increases in lipid peroxide concentrations were also observed in plasma of whitefish fed the high dose diet on day 31, but were not observed on day 104. These biochemical responses to dietary Ni require further evaluation. To evaluate exposure of natural populations of fish to Ni, analysis of Ni in kidney and liver and assessment of renal and hepatic histopathology are recommended for use in field bio-monitoring programs.

Nickel-based alloys have been in use since the 1930s; however, there are concerns regarding the release of metal ions (Be(+2), Cr(+6), Cr(+3), Ni(+2), Mo(+6)) from these alloys into surrounding tissues. Therefore, the objective of this study was to determine the cellular location and accumulation of ions using atomic absorption spectroscopy and correlate location with the cytotoxic, morphologic, and ultrastructural evaluations reported previously. Human gingival fibroblasts were exposed to the metal ions for 72 h. Controlled atomic absorption spectroscopy studies were used to determine the intracellular location of these ions reported as parts per million metal ions per milligram protein. Enzymatic markers were shown to correspond to the appropriate fraction indicating success in fractionation of the gingival fibroblasts. These results correspond with the cytotoxic, morphologic, and ultrastructural alterations reported previously for fibroblasts exposed to these ions. The highest concentration of beryllium ions occurred in the low-density molecule fraction, where lipofuscin granules were found, which has been shown to contain metal ions. The highest concentrations of hexavalent chromium ions occurred in the plasma membrane and nuclear fractions followed by the mitochondria fraction, which is supported by the ions' ability to oxidize to trivalent chromium accumulating at the membrane as well as the alterations in nuclear and mitochondrial function. For trivalent chromium, the highest concentrations occurred in the low-density molecule and the plasma membrane fractions, which correlates with the ions' inability to readily cross membranes. The highest concentration of molybdenum ions occurred in the plasma membrane fraction correlating with alterations in membrane morphology and increased numbers of myelin figures. The highest concentration of nickel ions was associated with the cytosol fraction where lipid droplets seen in the transmission electron micrographs were located. The current study demonstrates that a successful subcellular fractionation was obtained on gingival fibroblasts and that the location of metallic ions within the fractions correlated with cellular alterations reported previously., (Copyright 2001 John Wiley & Sons, Inc.)

Humans are exposed to carcinogenic nickel (Ni) compounds both occupationally and environmentally. In this paper, molecular mechanisms of nickel carcinogenesis are considered from the point-of-view of the uptake of nickel sulfide particles in cells, their dissolution and their effects on heterochromatin. Molecular mechanisms by which nickel induces gene silencing, DNA hypermethylation and inhibition of histone acetylation, will be discussed.

As a result of isotopic dilution, the availability to plants of radioisotopes introduced into the soil solution should be directly related to the size of the isotopically exchangeable pool (E(t))-value). This work was undertaken to test this hypothesis for the radionuclide 63Ni. The demonstration was based on pot experiments conducted with seven soils representing a large range of Ni content (from 9.9 mg kg(-1) to 862.6 mg kg(-1)) which were mixed with a 63NiCl2 solution (100 kBq kg(-1)). Three plant species varying in Ni uptake, Triticum aestivum (wheat), Trifolium pratense (clover), and the Ni-hyperaccumulator Alyssum murale, were grown for 90 d, and their total Ni and 63Ni content determined at harvest. In parallel, the isotopically exchangeable kinetics method (IEK) was run on each soil sample to measure the E(t)-value. Results showed that plant uptake of radioactive nickel was negatively correlated with the E(t)-value with wheat and clover as a result of the dilution of 63Ni added in the isotopically exchangeable pool of soil Ni (alpha=5%); correlation was positive with the A. murale (alpha=10%). Hence, this provides a new approach for the assessment of soil-to-plant transfer of 63Ni at larger scale avoiding the carrying out of time consuming experiments.

Bioaccumulation and biosorption of various nickel salts by Serratia marcescens (NCIM 2078) were investigated Biosorption of nickel was found maximum for the nickel nitrate and nickel chloride as 28.08 and 25.51 mg-1 nickel was obtained in dry biomass of S. marcescens, respectively. The possible role of pigment prodigiosin in uptake of nickel is discussed.

Alfalfa plants were grown in soil-pots contaminated with a mixture of Cd(II), Cu(II), Ni(II), and Zn(II), (at 50 mg/kg each) at pHs of 4.5, 5.8, and 7.1. The plants were fertilized using a nutrient solution, which was adjusted appropriately to the same pH. Plants in the control treatment were grown in the absence of the heavy metals mixture. The growth of the control plants was the same at the three pHs studied and the heavy metal stressed plants also showed similar behavior at each pHs. There were statistically significant differences (P<0.05) between the shoot length of the control treatment plants and the length of plants grown in the presence of the heavy metal mixture. Under the effects of the heavy metal mixture, nickel was the most accumulated element in the shoot tissue, with 437, 333, and 308 ppm at pH 7.1, 5.8, and 4.5, respectively. Cadmium was found to be second in accumulated concentrations with 202 ppm, 124 ppm, and 132 ppm at pH 7.1, 5.8, and 4.5, respectively, while zinc was third, followed by copper. The maximum relative uptakes (element in plant/element in soil-water-solution) were found to be 26 times for nickel, 23 times for cadmium, 12 times for zinc. and 6 times for copper. We considered these relations as indicative of the ability of alfalfa plants to take up elements from a soil matrix contaminated with a mixture of cadmium, copper, nickel, and zinc.

We adapted our mouse model of allergic contact hypersensitivity to nickel for the study of tolerance. Sensitization in this model is achieved by the administration of nickel ions with H(2)O(2); nickel ions alone are unable to prime naive T cells, but can restimulate primed ones. A 4-wk course of oral or i.p. administration of 10 mM NiCl(2) to naive mice induced tolerance, preventing the induction of hypersensitivity for at least 20 wk; long term desensitization of nickel-sensitized mice, however, required continuous NiCl(2) administration. When splenic T cells of orally tolerized donors, even after a treatment-free interval of 20 wk, were transferred to naive recipients, as with lymph node cells (LNC), they specifically prevented sensitization of the recipients. The LNC of such donors were anergic, because upon in vivo sensitization with NiCl(2) in H(2)O(2) and in vitro restimulation with NiCl(2), they failed to show the enhanced proliferation and IL-2 production as seen with LNC of mice not tolerized before sensitization. As few as 10(2) bulk T cells, consisting of both CD4(+) and CD8(+) cells, were able to specifically transfer tolerance to nickel. A hypothesis is provided to account for this extraordinarily high frequency of nickel-reactive, suppressive T cells; it takes into account that nickel ions fail to act as classical haptens, but form versatile, unstable metal-protein and metal-peptide complexes. Furthermore, a powerful amplification mechanism, such as infectious tolerance, must operate which allows but a few donor T cells to tolerize the recipient.

The aim of this study was to evaluate the concentrations of nickel and chromium ions in salivary and serum samples from patients treated with fixed orthodontic appliances. A second aim of this study was to determine any significant changes in these concentrations during any period of the treatment time. Saliva and blood samples were collected from 100 patients ranging in age from 12 to 33 years. Twenty samples from each group were obtained. The groups were as follows: In the first group, saliva and blood samples were collected before insertion of the fixed appliances. In the second, third, fourth, and fifth groups, samples were collected at 1 week, 1 month, 1 year, and 2 years after appliance insertion. The serum was prepared by centrifuging the blood samples at 3000 rpm for 10 minutes. The fixed appliances consisted of an average of 4 bands and 20 bonded brackets. No palatal or lingual appliances welded to bands or extraoral auxiliary appliances were used. The spectrophotometric determinations were carried out using electrothermal atomic absorption spectrophotometry. The results indicated certain differences in the amounts of nickel and chromium released from fixed orthodontic appliances during different periods of treatment. The Mann-Whitney U-test from the SPSS statistics program was used to analyze the significance of the differences between no-appliance samples and those obtained with the appliances present. In the serum, there were statistically significant increases in ion concentration in the second-year groups. In saliva samples, nickel and chromium reached their highest levels in the first month and decreased to their initial level in the rest of the groups. It can be concluded that fixed orthodontic appliances release measurable amount of nickel and chromium when placed in the mouth, but this increase doesn't reach toxic levels for nickel and chromium in the saliva and serum.

Objectives: To assess the exposure to tungsten, cobalt, and nickel in a plant producing hard metals. The main components of hard metals are tungsten carbide and cobalt metal. According to recent studies, these two components may be responsible for both fibrogenic and carcinogenic effects., Methods: 87 workers were investigated (86 male, one female) with a median age of 42 (range 22-58) and a mean duration of exposure of 13 years (range 1-27 years). Stationary and personal air sampling, and biological monitoring were carried out., Results: Ambient monitoring yielded maximum tungsten concentrations of 417 microg/m3 in the production of heavy alloys. A maximum cobalt concentration of 343 microg/m3 and a maximum nickel concentration of 30 microg/m3 were found at the sintering workshop. The highest urinary cobalt concentrations were found in the powder processing department. The mean concentration was 28.5 microg/g creatinine and the maximum value was 228 microg/g creatinine. The maximum nickel concentration in urine of 6.3 microg/g creatinine was detected in the department producing heavy alloys. The highest tungsten concentrations excreted in urine were found in grinders and had a mean value of 94.4 microg/g creatinine and a maximum of 169 microg/g creatinine. Due to the different solubility and bioavailability of the substance, there was no correlation between the tungsten concentrations in air and urine on a group basis., Conclusions: Despite its low solubility, tungsten carbide is bioavailable. The different bioavailability of tungsten metal and tungsten compounds has to be considered in the interpretation of ambient and biological monitoring data in the hard metal producing industry. The bioavailability increases in the order: tungsten metal, tungsten carbide, tungstenate. Only if both monitoring strategies are considered in combination can a valid and effective definition of high risk groups be derived.

Phytoremediation has shown great potential as an alternative treatment for the remediation of heavy-metal-contaminated soils and groundwater. However, the lack of a clear understanding pertaining to metal uptake/translocation mechanisms, enhancement amendments, and external effects on phytoremediation has hindered its full-scale application. The objective of this research was to investigate the ability of synthetic chelators for enhancing the phytoremediation of cadmium-, chromium- and nickel-contaminated soil. Ethylenediaminetriacetic acid (EDTA) and N-(2-hydroxyethyl)-ethylenediaminetriacetic acid (HEDTA) were applied to the soil at various dosages to elevate metal mobility. Uptake into and translocation within Helianthus annuus was determined. It was found that EDTA at a rate of 0.5 g/kg significantly increased the shoot concentrations of Cd and Ni from 34 and 15 to 115 and 117 mg/kg, respectively. The total removal efficiency for EDTA was 59 microg/plant. HEDTA at the same application rate resulted in a total metal uptake of 42 microg/plant. These research demonstrated that chelator enhancement is plant- and metal-specific and is subjective to inhibition when multiple heavy metals are present. Results also showed that chelator toxicity reduced the plant's biomass, thereby decreasing the amount of metal accumulation.

An 18-day experiment was conducted to investigate the uptake and sublethal toxicity of dietary Ni in adult lake whitefish (LWF, Coregonus clupeaformis) and lake trout (LT, Salvelinus namaycush) fed diets containing 0, 1000 and 10000 microg Ni/g, prepared with and without brine shrimp. The results of this experiment were used to design an experiment of longer duration in which one of the fish species was selected and exposed to lower dietary Ni doses. In the present study feed refusal was observed in LT and LWF fed 10000 microg Ni/g, after three and 4-5 feedings, respectively. LT fed Ni-contaminated diets exhibited different patterns of Ni accumulation than LWF. Increased Ni concentrations in all LWF tissues, except the intestine, were associated with increased doses of Ni. Copper and Zn concentrations in kidney and liver of LWF were altered. Metallothionein concentrations in kidneys of LT fed 1000 microg Ni/g and 10000 microg Ni/g and LWF fed 10000 microg Ni/g and in livers of LWF fed 10000 microg Ni/g (diet without shrimp only) increased significantly. Increased lipid peroxide production in the plasma of LT fed 10000 microg Ni/g was observed. Blood glucose and electrolytes were affected by Ni exposure. Histopathological alterations were observed in kidneys of LWF fed low and high dose diets, livers of whitefish fed high dose diets, and intestines of LWF fed high dose diets and LT fed low and high dose diets. LT fed high dose diets exhibited significant decreases in weight.

Superelastic Ni-Ti wire is widely used in orthodontic clinics, but delayed fracture in the oral cavity has been observed. Because hydrogen embrittlement is known to cause damage to Ti alloy systems, orthodontic wires were charged with hydrogen using an electro-chemical system in saline. Tensile tests were carried out, and fracture surfaces were observed after hydrogen charging. The strength of the Co-Cr alloy and stainless steel used in orthodontic treatment, was not affected by the hydrogen charging. However, Ni-Ti wire showed significant decreases in strength. The critical stress of martensite transformation was increased with increasing hydrogen charging, and the alloy was embrittled. The fractured surface of the alloys with severe hydrogen charging exhibited dimple patterns similar to those in the alloys from patients. In view of the galvanic current in the mouth, the fracture of the Ni-Ti alloys might be attributed to the degradation of the mechanical properties due to hydrogen absorption.

A review of the molecular mechanisms of nickel carcinogenesis has been compiled. This work is based upon approximately 20 years of research conducted in my laboratory. Molecular mechanisms of nickel carcinogenesis are considered from the point-of-view of the uptake of nickel, both soluble and insoluble particles in cells, its dissolution and its effects on heterochromatin. Molecular mechanisms by which nickel induces gene silencing in cells by DNA hypermethylation in mammalian cells and by inhibiting histone acetylation in yeast cells are also discussed.

A previously developed dosimetry model of inhaled Ni compounds in the human lung has been expanded by incorporating three additional factors: (1) inhalability, (2) mixed breathing mode, and (3) clearance rate coefficient of a Ni compounds' mixture. Predicted lung burdens of Ni compounds from the expanded model for workers at different departments in a Ni refinery plant compared favorably with the reported data. Although many uncertainties remain, the present model represents a first step toward developing a more meaningful risk assessment tool that will allow for more accurate extrapolation of animal data to humans., (Copyright 2001 Academic Press.)

Three trace heavy metals viz., nickel, copper and zinc were studied for their toxic action against Poecilia retriculata (Peters). Among these, copper was found to be most active followed by zinc and nickel. Accumulations of these metals as well as behavioural studies were carried out after exposing fish to sub-lethal concentration of LC20. It was found that the highest quantity of nickel was accumulated in the fish body followed by zinc and copper. After exposure to sub-lethal concentration of metals some behavioural changes in fish were observed due to stress, such as mucus like secretion over gills, excessive excretion, anoretic condition and increased distance between gills and operculum. In all the cases fin movement was observed. Role and use of such changes as biological indicators or as biological early warning system in water quality assessment has been discussed.

Twelve aerobic bacteria from activated sludge were isolated and identified. These included both Gram-positive (e.g., Bacillus) and Gram-negative (e.g., Pseudomonas) bacteria. The biosorption capacity of these strains for three different heavy metals (copper, nickel, and lead) was determined at pH 5.0 and initial metal concentration of 100 mg/L. Among these 12 isolates, Pseudomonas pseudoalcaligenes was selected for further investigation owing to its high metal biosorption capacity. The lead and copper biosorption of this strain followed the Langmuir isotherm model quite well with maximum biosorption capacity (q(max)) reaching 271.7mg of Pb2+/g of dry cell and 46.8 mg of Cu2+/g of dry cell at pH 5.0. Study of the effect of pH on lead and copper removal indicated that the metal biosorption increased with increasing pH from 2.0 to 7.0. A mutual inhibitory effect was observed in the lead-copper system because the presence of either ion affected the sorption capacity of the other. Unequal inhibitions were observed in all the nickel binary systems. The increasing order of affinity of the three metals toward P. pseudoalcaligenes was Ni < Cu < Pb. The metal biosorptive potential of these isolates, especially P. pseudoalcaligenes, may have possible applications in the removal and recovery of metals from industrial effluents.

Small-scale element distribution in soil-plant-systems in patches of Empetrum nigrum (microsites) at heavy metal contaminated sites located 0.5 and 4 km from the copper-nickel smelter at Harjavalta was investigated. The Cu concentrations of E. nigrum varied between 12 and 2300 mg/kg dw and showed increasing accumulation with increasing tissue age. Stems contained more Cu than leaves of the same age. The distribution pattern of Ni and Pb in the above-ground biomass followed that of Cu. Roots contained relatively low concentrations of all airborne heavy metals. In the soil, the highest concentrations of total Cu occurred in the humus (Oh) layer: on average 49,450 mg/kg dw at 0.5 km distance and 12,025 mg/kg dw at 4.0 km. Despite the extremely high Cu concentrations in the topsoil, the concentrations in the mineral soil below a depth of 10 cm did not exceed 2.5 mg/kg dw at any site.

Empetrum nigrum L. (crowberry) is one of the plants surviving near the Cu-Ni smelters in Finland and Russia. According to field observations, the fine roots of E. nigrum are situated below 40 cm depth and the root biomass is reduced in the polluted sites. This could cause a reduced root uptake of macronutrients and trace elements in the field and, therefore, the possible element uptake by aboveground parts of E. nigrum was studied in a greenhouse. Six different treatment solutions containing various heavy metal and macronutrient concentrations were applied to the stems and leaves of E. nigrum and the chemical composition and ecophysiological parameters were measured. Heavy metal concentrations in the leaves and stem bark, and Cu concentrations in the stems, increased with increasing metal concentrations in the spraying solutions. The bark and leaves had higher heavy metal concentrations than the stems of comparable age classes. The macronutrient and Mn concentrations in E. nigrum did not change significantly with increasing element concentrations in the spraying solution. Neither the stem water potential nor the leaf chlorophyll concentrations showed any clear response to element applications. Therefore, the element uptake by aboveground parts of E. nigrum was not confirmed by this study. However, there was a tendency to a decrease in CO2 exchange rate and increase in foliar abscisic acid content in plants treated with the highest element concentrations.

Two living Chlorella species were used to remove nickel from solution containing 30 micrograms Ni ml-1 in 10 successive cycles. The present study also examined the continued viability of these two algal species after repeated exposure to nickel. The two species of Chlorella were Chlorella vulgaris (commercially available) and WW1 (indigenous species isolated from domestic sewage and was tentatively identified as Chlorella miniata). The nickel removal percentage of WW1 cells was maintained at around 85% in the first five cycles, then declined slightly from the fifth cycle onwards, and finally achieved around 70% removal at the end of the 10th cycle. On the contrary, the removal efficiency of C. vulgaris declined from 50 to 30% during the 10 cycles of nickel bisorption. At the end of these 10 successive cycles, WW1 accumulated a substantial amount of Ni2+ (the cumulative cellular Ni concentration was 0.92% dry w.), while the value was only 0.17% in the case of C. vulgaris. These results suggest that the local isolate, WW1, had more consistent and satisfactory ability for removing Ni than the commercial C. vulgaris. Both algal species were still capable of dividing after each nickel treatment cycle, suggesting that the cells were not killed even when significant amounts of nickel were adsorbed/absorbed. However, Ni exposure adversely affected the physiological activity of algal cells as reflected by the decline in division rate and chlorophyll-a activity in both species. Such negative effects became more obvious as the number of cyclic treatments was increased. Nevertheless, WW1 cells appeared to recover from nickel treatment when re-cultivated in commercial medium for 2 weeks.

Hyperaccumulated Ni can defend plant tissues against herbivores and pathogens. The effectiveness of this defense, however, has not been tested with a viral pathogen. Turnip mosaic virus (TuMV) accumulation was studied in two serpentine species of Streptanthus with different Ni uptake abilities. Plants of a Ni hyperaccumulator, milk-wort jewelflower (S. polygaloides Gray), and a non-hyperaccumulator, plumed jewelflower (S. insignis Jepson), were grown on Ni-amended and unamended soils. Plants were inoculated with TuMV at three different phenological stages: basal rosette, bolting, and flowering. Susceptibility of experimental plants to TuMV was determined either by the magnitude of TuMV accumulation (measured by indirect enzyme-linked immunosorbent assay [ELISA]) or by plant survival. Streptanthus polygaloides plants grown on high-Ni soil were more susceptible to TuMV than low-Ni S. polygaloides at all three phenological stages. All rosette and pre-bolt S. insignis plants were infected by TuMV, but survival and TuMV accumulation were not significantly affected by soil Ni. At flowering, only high-Ni S. polygaloides plants became infected. For S. polygaloides, elevated tissue Ni concentrations enhanced TuMV infection instead of defending plants from the virus. To reduce risks to nearby agricultural crops, future phytoremed. iation and phytomining operations using this species should incorporate management plans to prevent the creation of artificial reservoirs of TuMV inoculum.

Bioaccumulation and chronic toxicity of nickel (Ni) to Hyalella azteca in Ni-spiked sediments was strongly affected by the source of sediment used. The total range in LC50s on a sediment concentration basis ranged over 20 fold. Differences in Ni toxicity generally matched differences in Ni bioaccumulation, and toxicity expressed on a body concentration basis varied less than three fold. Body concentrations, therefore, provide a much more reliable prediction of Ni toxicity in sediments than do concentrations in the sediment. Ni in overlying water was also a reliable predictor of Ni toxicity, but only in tests conducted in Imhoff settling cones with large (67:1) water to sediment ratios. Overlying water LC50s for tests in beakers varied 18 fold. Sediment and body concentrations of Ni tolerated by Hyalella were slightly higher in cones than in beakers. Reproduction was not affected significantly by Ni at concentrations below the LC50 and 10-week EC50s for survival and biomass production (including survival, growth and reproduction) were only marginally lower than 4-week EC50s (survival and growth only).

Biogeochemical cycles of Ni and Cu in pine forests on the northern tree line (Kola peninsula) in the background and industry-disturbed areas have been investigated. Total, bio-available and exchangeable concentrations of Ni and Cu in the soil, atmospheric Ni and Cu fluxes and soil water migration, and metal uptake by plants are considered. In the polluted area, forest ecosystems are seen as biogeochemical barriers which may attenuate intensity of Ni and Cu migration down the soil profile. A quantitative assessment is given of the role of dominating forest plants and soil horizons as barriers to heavy metal fluxes.

Previously, we found that nickel (Ni) accumulation by rat hepatocytes involves Ca channel transport processes. However, other mechanisms responsible for Ni accumulation are still unclear. Therefore, in the present study we examined the effects of sulfhydryl (SH) blockers on Ni accumulation by hepatocytes. Hepatocytes were exposed to various concentrations of N-ethylmaleimide (NEM) (0.5, 1 or 2 mM) or monoiodoacetic acid (MIA) (0.1, 0.25 or 0.5 mM), potent blockers of SH ligands, for 30 min and subsequently exposed to 10 microM NiCl(2) for an additional 60 min. Pretreatment with NEM and MIA enhanced the Ni accumulation by hepatocytes to maximum of 156 and 73%, respectively. The effects of essential and nonessential metal ions on Ni accumulation were also investigated. Pretreatment with 10 microM of Cu, Zn, Co, Cd and Mn, decreased Ni accumulation by 46, 30, 20, 18 and 11%, respectively. In contrast, pretreatment with Hg (10 and 20 microM) enhanced the Ni accumulation by almost 81 and 140%, respectively. Furthermore, significant decrease in SH concentration in the hepatocyte membrane was observed by the treatment with NEM, MIA and Hg, but not with Cu, Zn and Cd. These results suggest that Ni accumulation by hepatocytes does not appear to be dependent on the SH carrier-mediated transport processes, and that to block the SH ligands in the plasma membrane may facilitate the Ni crossing of the cell membrane.

The cell walls of plants, including those of algae, have the capacity to bind metal ions in negatively charged sites. The authors had already shown that the wild type (walled) strain of the unicellular green alga Chlamydomonas reinhardtii Dangeard was more tolerant to Cd, Co, Cu, and Ni than a wall-less mutant of the same species. The objective of the present study was to determine if the tolerance to metals was associated with an increased adsorption of the same metals to the cell wall. Adsorbed metal was defined as that fraction that could be removed with a solution containing Na(2)EDTA and CaCl(2). The fraction that remained after the EDTA/CaCl(2) wash was considered to be strongly bound in the cell. When exposed to metals, singly, in solution for 24 h, cells of both strains accumulated the metals. The original hypothesis was supported by the results for Cd, Co, and Ni insofar as significantly higher concentrations of these metals were in the loosely bound fraction of the walled strain in comparison with the wall-less strain. However, there are three reasons why the potentially protective effect of the cell wall did not explain differential tolerance of the two strains. After 24 h of exposure (1) less Cd was accumulated internally by the wall-less strain than by the walled strain, (2) very little of the accumulated Cu was in the loosely bound fraction of the walled strain, and (3) the two strains accumulated comparable and relatively high amounts of internal Cu. Unexpectedly, significant amounts of Cd and Cu were also removable from the surface of the wall-less cells. One possible explanation for these apparently externally bound metals in the wall-less strain is that the cells exuded metal-chelating molecules that decreased the ability of metal ions to penetrate the plasma membrane. It was concluded that metal tolerance in this alga must involve a complex of mechanisms involving both internal and external detoxification of metal ions.

A series of batch experiments was conducted to compare the ability of 11 microalgal species of the same cell density in removing nickel (Ni) and zinc (Zn) from synthetic wastewater. These included Chlorella vulgaris (commercially available), Chlorella sorokiniana and Scenedesmus quadricauda (isolates from polluted water of Wuhan, China), and eight different isolates from Hong Kong. The Wuhan isolate of Scenedesmus removed most Ni, probably due to its large biomass. Nickel concentration was reduced from an initial 30 to 0.9 mg/l after 5 min (97% Ni removal), and further declined to 0.4 mg/l after 90 min of treatment. In wastewater containing 30 mg/l Ni and 30 mg/l Zn, more than 98%, Ni and Zn were removed simultaneously at the end of 5 min treatment, indicating that the presence of Zn in wastewater did not affect Ni removal by this Scenedesmus isolate. The second most effective species for Ni removal was an isolate, tentatively identified as Chlorella miniata, Ni concentration was reduced to 10 mg/l after 90 min, and was only slightly interfered by the presence of Zn. In terms of metal removal per unit biomass or unit surface area of algal cells, C. miniata was the best species in removing Ni and Zn. At the other extreme, one Hong Kong isolate (Synechocystis sp.) did not remove any Ni and only achieved 40% Zn removal. Performance of the other isolates was comparable with the commercial C. vulgaris, less than 50% Ni was removed after 5 h of treatment and Ni removal was significantly reduced by the presence of Zn. All algae tested were found to be viable, showing these 11 species could tolerate a mixture of 30 mg/l Ni and 30 mg/l Zn in wastewater.

Escherichia coli actively imports nickel via the ATP-dependent NikABCDE permease. NikR, a protein of the ribbon-helix-helix family of transcription factors, represses expression of the nikABCDE operon in the presence of excessive concentrations of intracellular nickel. Here, the NikR operator site is identified within the nikABCDE promoter by footprinting and mutational analyses. The operator consists of two dyad-symmetric 5'-GTATGA-3' recognition sequences separated by 16 base pairs. Mutations in the GTATGA sequences reduce NikR binding affinity in vitro and reduce repression of a P(nik)-lacZ fusion in vivo. Moreover, NikR is shown to be a direct sensor of nickel ions. Strong operator binding requires the continual presence of 20-50 micrometer nickel, indicating the presence of a low affinity nickel-binding site, and NikR dimers also contain two high affinity nickel-binding sites. In addition to both GTATGA sites and nickel, high affinity operator binding also requires the C-terminal domain of NikR.

Motor neurons innervating tiny muscles in the antennal system of the cockroach, Periplaneta americana, were stained by two new approaches to backfilling motor axons and somata. Both methods are easier, and produce less leakage of dye, than conventional methods that rely on application of dye to the distal cut end of a motor nerve or immersion of a whole muscle in dye. One approach used here was to pressure-inject nickel (or cobalt) chloride directly into a muscle from a micropipette. The other was to place filter paper soaked in nickel chloride on the muscle surface. The first approach enabled staining of motor neurons most reliably and with preservation of stain to the specific muscle of interest. The second approach had different advantages: it was easier to perform, resulted in more intense staining and frequently more complete staining of dendritic structure than the first approach. Taken together, these two approaches should prove useful for tracing motor circuits in a number of model systems.

The aim of this work was to study the absorption of nickel chloride in rats by means of the intestinal perfusion in situ technique at nickel concentrations of 1, 5, 10, 25, and 100 mg/L. Active transport and facilitated diffusion seem to play an important role in the intestinal absorption of nickel at concentrations < or = 10 mg/L. At higher concentrations, the absorption rate would be limited by saturation of the carriers. The distribution of the absorbed nickel was studied by intestinal perfusion of a 10-mg Ni/L solution for 30 or 60 min. Both in concentration and amount, the jejunum showed the higher values of absorbed nickel, followed by the kidneys and liver. When all of the collected organs (brain, heart, liver, lungs, spleen, kidneys, and testicles) and blood, but not the small intestine, are analyzed following a 60-min perfusion, it was found that 1% of the initial concentration had passed through the intestinal barrier.

A substantial body of occupational epidemiology data has shown that exposure to mixed soluble and insoluble nickel causes the development of lung and nasal cancer. However, due to coexposure of these populations to soluble and insoluble forms of nickel, and limitations in exposure measurements, the contribution of soluble nickel is difficult to determine. Soluble nickel was negative in an NTP inhalation bioassay, while there was some evidence for tumorigenicity in rats for less soluble nickel oxide, and there was clear evidence for tumorigenicity of insoluble nickel subsulfide in rats. Results of parenteral assays follow a similar pattern, but provide evidence of weak carcinogenicity of soluble nickel. Kinetic factors also indicate that exposure to soluble nickel alone has a low carcinogenic potential. Overall, we conclude that the carcinogenic activity of insoluble nickel compounds should not be used to predict the carcinogenic potential of water-soluble nickel salts. The overall data suggest a nonlinear dose-response relationship for carcinogenicity, but the data are insufficient to determine the doses at which such nonlinearities occur. Under the U.S. EPA's 1996 proposed "Guidelines for Carcinogen Risk Assessment," inhaled soluble nickel compounds would be classified as "cannot be determined," because the existing evidence is composed of conflicting data. A reference concentration of 2 x 10(-4) mg Ni/cu x m was calculated, based on lung fibrosis in male rats observed in the NTP study.

Nitric oxide is an important bioactive signaling molecule that mediates a variety of normal physiological functions which, if altered, could contribute to the genesis of many pathological conditions, including diabetes. In the present study we have shown the involvement of NO in nickel-induced hyperglycemia in male albino rats. Administration of nickel chloride (25 to 100 micromol/kg; ip) to overnight-fasted rats resulted in significant dose and time-dependent increase in plasma glucose, attaining maximum level at 1 h posttreatment and thereafter decreasing to normal levels by 4 h. The involvement of NO in nickel-induced hyperglycemia was evident by the observation that pretreatment of rats with NG-monomethyl-l-arginine (10 to 50 micromol/kg; ip), an inhibitor of nitric oxide synthase (NOS), significantly attenuated the nickel-mediated increase in the plasma glucose levels in a dose-dependent fashion. The activity of Ca(2+)-dependent NOS (constitutive form, c-NOS) was found to be significantly elevated in adrenals (5.5-fold) and brain (1.4-fold) at 1 and 2 h posttreatment, attaining normal levels by 4 h. In contrast, the activity of c-NOS in pancreas was significantly decreased (2.8-fold) with a concomitant increase (11.6-fold) in inducible NOS (i-NOS) at the same time interval. As observed by immunoblot analysis, a significant increase in i-NOS protein expression in the pancreas was observed at 1 and 2 h posttreatment. This was associated with a significant elevation in cGMP levels in adrenals, brain, and pancreas, possibly via the stimulation of cytosolic guanylate cyclase. This elevation in cGMP was abolished by low concentration of hemoglobin. These effects were associated with the accumulation of nickel in the target tissues. Taken together, our data suggest that nickel causes a significant increase in the levels of (i) cGMP and c-NOS in adrenals and brain and (ii) i-NOS in pancreas. These events may be responsible for modulating the release of insulin from pancreas finally leading to hyperglycemic condition in rats., (Copyright 2000 Academic Press.)

Understanding how animals are exposed to the large repository of metal pollutants in aquatic sediments is complicated and is important in regulatory decisions. Experiments with four types of invertebrates showed that feeding behavior and dietary uptake control bioaccumulation of cadmium, silver, nickel, and zinc. Metal concentrations in animal tissue correlated with metal concentrations extracted from sediments, but not with metal in porewater, across a range of reactive sulfide concentrations, from 0.5 to 30 micromoles per gram. These results contradict the notion that metal bioavailability in sediments is controlled by geochemical equilibration of metals between porewater and reactive sulfides, a proposed basis for regulatory criteria for metals.

Recently we discovered a tobacco protein (designated NtCBP4) that modulates heavy-metal tolerance in transgenic plants. Structurally, NtCBP4 is similar to mammalian cyclic-nucleotide-gated non-selective cation channels containing six putative transmembrane domains, a predicted pore region, a conserved cyclic-nucleotide-binding domain, and a high-affinity calmodulin-binding site that coincides with its cyclic-nucleotide-binding domain. Transgenic tobacco expressing the plasma-membrane-localized NtCBP4 exhibit improved tolerance to Ni(2+) and hypersensitivity to Pb(2+), which are associated with a decreased accumulation of Ni(2+) and an enhanced accumulation of Pb(2+) respectively. Transgenic plants expressing a truncated version of NtCBP4, from which regulatory domains had been removed, have a different phenotype. Here we describe our approach to studying the involvement of NtCBP4 in heavy-metal tolerance and to elucidate its physiological role.

The transition metal Ni is an essential cofactor for a number of enzymatic reactions in both prokaryotes and eukaryotes. Molecular analyses have revealed the existence of two major types of high-affinity Ni2+ transporters in bacteria. The Nik system of Escherichia coli is a member of the ABC transporter family and provides Ni2+ ion for the anaerobic biosynthesis of hydrogenases. The periplasmic binding protein of the transporter, NikA, is likely to play a dual role. It acts as the primary binder in the uptake process and is also involved in negative chemotaxis to escape Ni overload. Expression of the nik operon is controlled by the Ni-responsive repressor NikR, which shows functional similarity to the ferric ion uptake regulator Fur. The second type of Ni2+ transporter is represented by HoxN of Ralstonia eutropha, the prototype of a novel family of transition metal permeases. Members of this family have been identified in gram-negative and gram-positive bacteria and recently also in a fission yeast. They transport Ni2+ with very high affinity, but differ with regard to specificity. Site-directed mutagenesis experiments have identified residues that are essential for transport. Besides these uptake systems, different types of metal export systems, which prevent microorganisms from the toxic effects of Ni2+ at elevated intracellular concentrations, have also been described.

Salmonella typhimurium CorA is the archetypal member of the largest family of Mg(2+) transporters of the Bacteria and Archaea. It contains three transmembrane segments. There are no conserved charged residues within these segments indicating electrostatic interactions are not used in Mg(2+) transport through CorA. Previous mutagenesis studies of CorA revealed a single face of the third transmembrane segment that is important for Mg(2+) transport. In this study, we mutated hydroxyl-bearing and other conserved residues in the second transmembrane segment to identify residues involved in transport. Residues Ser(260), Thr(270), and Ser(274) appear to be important for transport and are oriented such that they would also line a face of an alpha-helix. In addition, the sequence (276)YGMNF(280), found in virtually all CorA homologues, is critical for CorA function because even conservative mutations are not tolerated at these residues. Finally, mutations of residues in the second transmembrane segment, unlike those in the third transmembrane segment, revealed cooperative behavior for the influx of Mg(2+). We conclude that the second transmembrane segment forms a major part of the Mg(2+) pore with the third transmembrane segment of CorA.