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PubMedDate not supplied

Mutagenic effects of some water-soluble metal compounds in a somatic eye-color test system in Drosophila melanogaster.

Nickel, cadmium, lead, arsenic, manganese and chromium salts as well as MeHgOH were screened for mutagenicity, using a sensitive somatic eye-color test system in Drosophila melanogaster. The test is based on the insertion of a mobile element which causes instability in the white locus that is somatically enhanced by mutagens. This white locus expression is combined with a mutation, zeste, in another gene, to produce a light yellow eye color. Larval feeding with mutagens causes somatic mutations in the eye imaginal disc cells that develop into easily detectable red spots in the yellow eyes of adult males. Survival tests showed large differences in the toxicity of different metals, but only hexavalent chromium increased the frequency of somatic mutations above the control level. When combined treatments were carried out with MMS and various metals, sodium arsenite caused a reduction of the MMS-induced mutation frequency while methylmercury increased the frequency of somatic spots.

Animals↗
PubMed2006

Oxidative stress and genotoxic effects in gill and kidney of Anguilla anguilla L. exposed to chromium with or without pre-exposure to beta-naphthoflavone.

Fish in the aquatic environment can be subjected to a multipollution state and the occurrence of sequential exposures is an important aspect of eco-toxicological research. In this context, a preceding exposure can affect a toxic response to a subsequent exposure. Therefore, the current study was based on sequential exposures, viz. to a PAH-like compound (beta-naphthoflavone, BNF) followed by a heavy metal (chromium, Cr), focusing on the assessment of oxidative stress responses and their role in induction of genotoxicity. Oxidative stress responses in gill and kidney were investigated in European eel (Anguilla anguilla L.), and measured as lipid peroxidation (LPO), glutathione peroxidase (GPX), catalase (CAT) and glutathione S-transferase (GST) activity, and reduced glutathione (GSH) concentration, whereas genotoxicity was measured as DNA strand breakage. Fish were exposed for 24 h to two Cr concentrations (100 microM, 1 mM), with or without pre-exposure to BNF (2.7 microM, 24 h). In gill, a GSH decrease was observed along with loss of DNA integrity at all exposure conditions except at the lowest Cr concentration, showing a crucial role of GSH over genotoxicity. Moreover, sporadic induction of antioxidant enzymes was not effective in the protection against genotoxicity. However, a different mechanism seems to occur in kidney, since the loss of DNA integrity detected for all exposed groups was not accompanied by alterations in antioxidant levels. With regards to peroxidative damage, both organs showed an LPO increase after sequential exposure to BNF and 100 microM Cr. However, no association between LPO induction and antioxidant responses could be established, showing that LPO is not predictable solely on the basis of antioxidant depletion. The interference of BNF pre-exposure with the response of organs to Cr showed a marked dependence on the Cr concentration. Gill showed synergistic effects on LPO and GPX increase, as well as on CAT and GSH decrease for the lowest Cr concentration. However, for the highest concentration an additive effect on decrease of DNA integrity and an antagonistic effect on the increase of GPX were observed. In kidney, synergistic effects were evident on LPO increase and GSH decrease for the lowest Cr concentration, as well as on CAT and GST decrease for the highest concentration. In contrast, an antagonistic action was observed on DNA integrity loss for both Cr concentrations. The current results are relevant in assessing the interactions of PAHs and metals and contribute to a better knowledge about oxidative stress and mechanisms of genotoxicity in fish.

Anguilla↗
PubMed1996

Characterization of porphyrin heme oxygenase inhibitors.

Synthetic metalloporphyrin derivatives of heme have been identified as competitive inhibitors of heme oxygenase, the rate-limiting enzyme in the heme degradation pathway that produces equimolar quantities of carbon monoxide, biliverdin, and bilirubin. Therefore, administration of metalloporphyrin has been proposed as one means to prevent excessive hyperbilirubinemia in human neonates. Tin proto- and meso-porphyrin have been studied for the suppression of neonatal jaundice. However, these compounds are also photosensitizers. This property may limit the clinical use of these compounds, particularly in infants being exposed simultaneously to phototherapy. Via measurements of carbon monoxide, we have studied the photooxidative, metabolic, and inhibitory characteristics of metalloporphyrins that have not yet been studied for this purpose: deuteroporphyrin bisglycol (DBG), iron deuteroporphyrin bisglycol (FeBG), tin deuteroporphyrin bisglycol (SnBG),tin deuteroporphyrin (SnDP), chromium deuteroporphyrin (CrDP), and zinc deuteroporphyrin (ZnDP). Of the six compounds, SnDP, SnBG, and DBG were significantly photoreactive in vitro. Furthermore, in vitro measurements of brain, liver, and spleen heme oxygenase activity inhibition indicated that, of the nonphotoreactive compounds, CrDP and ZnDP were the most potent inhibitors. Only FeBG served as a substrate for the heme oxygenase reaction. The concentration for 50% inhibition with the three tissues ranged from 0.6 to 1.3 microM for CrDP and from 11.0 to 13.5 microM for ZnDP. When 25 mumol CrDP and 50 mumol ZnDP per kilogram body weight were administered to rats given a heme load of 30 mumol/kg body weight, the total body carbon monoxide excretion due to the administered heme load was reduced by 46 and 32%, respectively, at t = 7.5 h, when the experiment was terminated in order to measure heme oxygenase activity. Brain heme oxygenase activity was not affected by the metalloporphyrin treatment. However, both CrDP and ZnDP inhibited liver tissue heme oxygenase activity to 5 and 20%, respectively, whereas only CrDP inhibited spleen tissue heme oxygenase, to 7% of untreated control. Thus, CrDP appears to be the most attractive of the six compounds and deserves further study.

Animals↗
PubMed1998

Chromium and zinc contamination of parenteral nutrient solution components commonly used in infants and children.

Chromium and zinc contamination of components of parenteral nutrient (PN) solutions used in infants and children was studied. Solutions of amino acids, L-cysteine hydrochloride, dextrose, electrolytes, minerals, vitamins, multiple trace elements, and individual trace elements were obtained. A variety of manufacturers, lots, and expiration dates were represented when possible. The solutions were analyzed for chromium and zinc by flame atomic absorption spectrophotometry. In all amino acid products, chromium concentration was below the limit of detection and zinc concentration ranged from 0.06 to 4.97 mg/L. In the L-cysteine hydrochloride products, chromium was measurable in only two lots (0.11 and 0.23 mg/L); zinc was measurable in all lots (32-86 mg/L). Sodium and potassium salts of chloride and acetate had chromium concentrations of 0.02-0.23 mg/L and zinc concentrations of 0.35-0.56 mg/L. Phosphate salts contained chromium 0.39-0.44 mg/L and zinc 0.91-2.33 mg/L. In calcium gluconate, zinc concentration was 0.28-2.38 mg/L. In four lots of multiple trace elements, chromium was 92-104% and zinc was 100-113.5% of the labeled amount. A PN solution for a < 10-kg infant compounded from the components assayed would provide up to an additional 0.7 microgram of chromium per kilogram and 200 micrograms of zinc per kilogram. Zinc and chromium contaminants were detected in many of the products that are common components of PN solutions for infants and children; the contamination may be sufficient to result in the administration of zinc and chromium in amounts exceeding current recommendations.

Child↗
PubMed1993

Effect of processing cement to concrete on hexavalent chromium levels.

Hexavalent chromium sensitization is known to occur from exposure to cement. Concrete is a mixture of cement, sand, rock, and water. Admixtures are compounds used to retard or accelerate concrete setting time. Some countries use ferrous sulfate to reduce hexavalent chromium in cement. We evaluated and compared hexavalent chromium levels in cement, rock (aggregate), and wet and dry concrete in samples from Singapore, Ireland, Denmark, Australia, and the United States. Cement from Denmark contains ferrous sulfate. The effect of representative admixtures on hexavalent chromium concentration in concrete was also evaluated, but technical limitations made evaluation difficult. Soluble chromium levels in cement ranged from 0.225 mg/kg in the US sample to 0.036 mg/kg in the Singapore sample. Aggregate chromium levels ranged from 0.083 mg/kg in the Denmark sample to < 0.002 mg/kg in the Ireland sample. Fresh US concrete, with 1.27 mg/kg hexavalent chromium, contained the highest level. The Denmark sample, with ferrous sulfate added, was lowest (< 0.01 mg/kg). Hardened concrete levels ranged from 0.104 mg/kg from the Ireland sample to 0.002 mg/kg from the Singapore sample. Therefore, hexavalent chromium levels do appear to be influenced by admixtures and by processing from powdered cement to dry concrete. Ferrous sulfate significantly reduced hexavalent chromium levels in fresh cement.

Carcinogens, Environmental↗
PubMed2005

Immobilization of glucose oxidase onto gelatin for biosensor construction.

The properties of a glucose biosensor made by immobilization of glucose oxidase onto gelatin in a layer of electrochemically deposited polyaniline have been investigated. Glucose oxidase was immobilized within gelatin cross-links with chromium(III) acetate. The glucose oxidase biosensor was developed by forming a polyaniline-deposited electrode surface as support for the immobilized enzyme gel, in order to increase its durability. The polyaniline/gelatin/glucose oxidase biosensor has been characterized using chemical and electrochemical methods. Temperature, pH, cross-linking agent concentration, enzyme concentration, kinetic properties, reusability and the effect of electro-active compounds were among the parameters studied. The response time of the glucose oxidase biosensor is 90 s, the detection limit is below 1 mmol/dm3 and the sensor can be used 20 times within a 2-month period without losing its stability.

Acetates↗
PubMed2006

Synthesis, structural characterization, and properties of chromium(III) complexes containing amidinato ligands and eta2-pyrazolato, eta(2)-1,2,4-triazolato, or eta1-tetrazolato ligands.

Treatment of anhydrous chromium(III) chloride with 2 or 3 equivalents of 1,3-di-tert-butylacetamidinatolithium or 1,3-diisopropylacetamidinatolithium in tetrahydrofuran at ambient temperature afforded Cr(tBuNC(CH3)NtBu)2(Cl)(THF) and Cr(iPrNC(CH3)NiPr)3 in 78% and 65% yields, respectively. Treatment of Cr(tBuNC(CH3)NtBu)2(Cl)(THF) with the potassium salts derived from pyrazoles and 1,2,4-triazoles afforded Cr(tBuNC(CH3)NtBu)2(X), where X=3,5-disubstituted pyrazolato or 3,5-disubstituted 1,2,4-triazolato ligands, in 65-70% yields. X-Ray crystal structure analyses of Cr(tBuNC(CH3)NtBu)2(Me2pz) (Me2pz=3,5-dimethylpyrazolato) and Cr(tBuNC(CH3)NtBu)2(Me2trz) (Me2trz=3,5-dimethyl-1,2,4-triazolato) revealed eta2-coordination of the Me2pz and Me2trz ligands. Treatment of Cr(tBuNC(CH3)NtBu)2(Cl)(THF) with trifluoromethyltetrazolatosodium (NaCF3tetz) in the presence of 4-tert-butylpyridine afforded Cr(tBuNC(CH3)NtBu)2(CF3tetz)(4-tBupy) in 30% yield. An X-ray crystal structure determination showed eta1-coordination of the tetrazolato ligand through the 2-nitrogen atom. The complexes Cr(iPrNC(CH3)NiPr)3 and Cr(tBuNC(CH3)NtBu)2(X) are volatile and sublime with <1% residue between 120 and 165 degrees C at 0.05 Torr. In addition, these complexes are thermally stable at >300 degrees C under an inert atmosphere such as nitrogen or argon. Due to the good volatility and high thermal stability, these new compounds are promising precursors for the growth of chromium-containing thin films using atomic layer deposition.

Journal Article↗
PubMed1998

Immunotoxicologic effects of inhaled chromium: role of particle solubility and co-exposure to ozone.

Soluble and insoluble hexavalent chromium (Cr6+) agents are concomitantly released with ozone (O3) during welding. Although pulmonary/immunologic implications from exposure to each agent individually have been investigated, the effects from simultaneous exposure, as occurs under actual working conditions, are unclear. To investigate immunomodulatory effects of inhaled Cr6+, F-344 rats were exposed for 5 h/day, 5 days/week for 2 or 4 weeks to atmospheres containing soluble potassium chromate (K2CrO4) or insoluble barium chromate (BaCrO4), each alone at 360 micrograms Cr/m3 or in combination with 0.3 ppm O3. One day after the final exposure, rats were euthanized, their lungs were lavaged, and pulmonary macrophages (PAM) were recovered for assessment of basal and inducible functions. Rats inhaling K2CrO4-containing atmospheres had greater levels of total recoverable cells, neutrophils, and monocytes in bronchopulmonary lavage compared to rats exposed to insoluble Cr6+ atmospheres, O3 alone, or air; these rats also had a reduced percentage of PAM, although total PAM levels remained unaffected. Although Cr exposure-related changes in PAM functionality were evident, any dependence upon Cr solubility was variable. K2CrO4-containing atmospheres modulated PAM-inducible interleukins-1 and -6, and tumor necrosis factor-alpha production to a greater degree than those containing BaCrO4. Conversely, BaCrO4-containing atmospheres affected PAM basal nitric oxide production and interferon-gamma-primed/zymosan-stimulated reactive oxygen intermediate production to a greater extent than did those containing K2CrO4. In none of the PAM assays did co-inhalation of O3 result in a modulation of the effects obtained with either Cr6+ compound itself. The results indicate that, while immunomodulatory effects of inhaled Cr6+ upon PAM are related to particle solubility, the co-inhalation of O3 apparently does not cause further modifications of the metal-induced effects.

Administration, Inhalation↗
PubMed2002

Ethylenediammonium bis[bis[N-(2-aminoethyl)glycinato-kappa(3)N,N',O]chromium(III)] tetrachloride dihydrate at 293 and 100 K.

The crystal structure of the title compound, (C(2)H(10)N(2))[Cr(C(4)H(9)N(2)O(2))(2)](2)Cl(4) x 2H(2)O, has been determined by single-crystal X-ray diffraction studies at 293 and 100 K. The analyses demonstrated that the crystal consists of ethylenediammonium dications (which lie about inversion centres), bis[N-(2-aminoethyl)glycinato]chromium(III) monocations, Cl(-) anions and hydrate water molecules, in a molecular ratio of 1:2:4:2. The complex cation unit has a slightly distorted octahedrally coordinated Cr atom, with two Cr[bond]O and four Cr[bond]N bonds in the ranges 1.951 (1)-1.953 (1) and 2.054 (1)-2.089 (2) A, respectively, at 293 K. The geometry of the bis[N-(2-aminoethyl)glycinato]chromium(III) moiety was found to be trans,cis,cis with respect to the carboxylate O atom and the primary and secondary amine N atoms. The two analyses, at 293 and 100 K, exhibited no remarkable structural differences, although the colour of the crystals did differ, being red at 293 K and orange at 100 K.

Journal Article↗
PubMed2002

Intracellular signal transduction of cells in response to carcinogenic metals.

Epidemiological and animal studies suggest that several metals and metal-containing compounds are potent mutagens and carcinogens. These metals include chromium, arsenic, vanadium, nickel, and others. During the last two decades, chemical and cellular studies have contributed enormously to our understanding of the mechanisms of metal-induced pathophysiological processes. Although each of these metals is unique in its mechanism of action, some common signaling molecules, such as reactive oxygen species (ROS), may be shared by many of the carcinogenic metals. New techniques are now available to reveal the mechanisms of carcinogenesis in precise molecular terms. In this review, we focused our attentions on carcinogenic metal-induced signal transduction pathways leading to the activation of NF-kappaB, cell apoptosis and cell cycle progression, three crucial steps or events involved in the transformation and carcinogenesis. This review summarizes current knowledge and our recent studies concerning intracellular signal transduction pathways initiated by carcinogenic metals and the cross-talk that occurs among these pathways in cells in response to metals.

Animals↗
PubMed1999

Synthesis and Structural Analysis of BaCrS(2).

A new ternary chromium sulfide, BaCrS(2), was synthesized. This solid state compound crystallizes in the orthorhombic, centrosymmetric space group Pmmn (No. 59) with a = 4.2606(6) Å, b = 4.7944(7) Å, c = 9.443(1) Å, V = 192.89(5) Å(3), and Z = 2. The solid is similar to a previously known structure BaNiS(2) in which the Ni atom is coordinated to five sulfur atoms in a square pyramidal fashion. In BaCrS(2), the square pyramid distorts such that the two S(basal)-Cr-S(basal) angles are no longer equal. Thus the BaCrS(2) solid is orthorhombic whereas BaNiS(2) is tetragonal. The distortion from the square pyramidal coordination in the title compound is traced to the broken degeneracy of the d(xy)() and d(xz)() set by a computational analysis.

Journal Article↗
PubMed1980

The neutral and acidic glyceroglucolipids from gastric mucous barrier of rat-stomach antrum, body and forestomach.

Distribution of glyceroglucolipids in the mucous barrier of rat-stomach antrum, body and forestomach was investigated. Surface mucus lining and preformed intracellular mucus were obtained by perfusion in vivo of the ligated stomach compartments wit saline and 2 M NaCl. Lipids were extracted from dialyzed and lyophilized samples, and separated on DEAE-Sephadex into neutral and acidic fractions. The glyceroglucolipids contained in each fraction were quantified and then separated into individual components by thin-layer chromatography. Significant differences in the concentration of glyceroglucolipids in the separated areas of the stomach were found. The content of glyceroglucolipids in the antral portion of the stomach was five-times greater than that of the forestomach. The level of sulfated glyceroglucolipids was eight-times greater in the antrum as compared to the body and four-times greater as compared to the forestomach. One sulfated glyceroglucolipid was present in antral perfusates, whereas the body and forestomach contained two additional acidic glyceroglucolipids. Based on data of partial acid and alkaline methanolyses, oxidation with periodate and chromium trioxide, and methylation of the native and desulfated compound, the structure of antral glyceroglucolipid is proposed to be: SO3H(leads to 6)Glc(alpha 1 leads to 6)Glc-(alpha 1 leads to 6)Glc(alpha 1 leads to 6)Glc(alpha 1 leads to 3)-1(3)-O-alkyl-2-O-acylglycerol. The neutral glyceroglucolipid fractions from each area of the stomach were similar in composition and only variations in their concentration were observed. The data obtained suggest that the sulfated glyceroglucolipids are involved in the protection of the gastric mucosa of the antrum, since their concentration is greatest in this most acidic portion of the stomach which is also most often exposed to duodenal reflux.

Animals↗
PubMed1999

Adherent surface mucus gel restricts diffusion of macromolecules in rat duodenum in vivo.

The aim of this study was to investigate the permeability of the adherent mucus gel layer in rat duodenum in vivo to macromolecules applied in the lumen. Rats were anesthetized with thiobarbiturate, and the duodenum was perfused with isotonic NaCl solution containing large-molecular-size secretagogues. Effects on mucosal HCO(-)(3) secretion and blood-to-lumen (51)chromium-labeled EDTA clearance were used as indexes that compounds had migrated across the mucus layer. Exposure to a low concentration of papain (10 U/100 ml) for 30 min removed the mucus layer without damage to the epithelium and induced or markedly enhanced HCO(-)(3) secretory responses to cholera toxin (molecular mass of 85 kDa) or glucagon (3.5 kDa). Water extracts from a VacA cytotoxin (89 kDa) producing Helicobacter pylori strain, but not from a toxin-negative isogenic mutant, caused a small increase in HCO(-)(3) secretion but only after the mucus layer had been removed by papain. The duodenal surface mucus gel thus significantly restricts migration of macromolecules to the duodenal surface. Release of bacterial toxins at the cell-mucus interface may enhance or be a prerequisite for their effects on the gastrointestinal mucosa.

Animals↗