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PubMed1997

Healthy environments for healthy people: bioremediation today and tomorrow.

Increases in environmental contamination lead to a progressive deterioration of environmental quality. This condition challenges our global society to find effective measures of remediation to reverse the negative conditions that severely threaten human and environmental health. We discuss the progress being made toward this goal through application of bioremediation techniques. Bioremediation generally utilizes microbes (bacteria, fungi, yeast, and algae), although higher plants are used in some applications. New bioremediation approaches are emerging based on advances in molecular biology and process engineering. Bioremediation continues to be the favored approach for processing biological wastes and avoiding microbial pathogenesis. Bioremediation may also play an increasing role in concentrating metals and radioactive materials to avoid toxicity or to recover metals for reuse. Microbes can biodegrade organic chemicals; purposeful enhancement of this natural process can aid in pollutant degradation and waste-site cleanup operations. Recently developed rapid-screening assays can identify organisms capable of degrading specific wastes and new gene-probe methods can ascertain their abundance at specific sites. New tools and techniques for use of bioremediation in situ, in biofilters, and in bioreactors are contributing to the rapid growth of this field. Bioremediation has already proven itself to be a cost-effective and beneficial addition to chemical and physical methods of managing wastes and environmental pollutants. We anticipate that it will play an increasingly important role as a result of new and emerging techniques and processes.

Animals↗
PubMed2000

Ruthenium-based compounds and tumour growth control (review).

Heavy metals have often been represented, as an uncertain entity related to renal and other risks of toxicity. In favour of this thought there are several lines of evidence, first of all traffic pollution, other evidence that metals such as arsenite, mercury, cadmium or even iron or radioactive heavy metals, that may be introduced into the body by accident, have been responsible of well known pathologies (for example saturnism with lead) or acute toxicity. Therefore, the biological and medical literature have debated on this subject, mainly from the toxicological point of view, rather than studying possible advantages that might come from compounds based on these metals. Exceptions are represented by studies on the role of metal ions in the biochemistry of enzymes and energy production and, although with less emphasis, on their possible use for correcting metabolic malfunctions. Ruthenium, as a metal, has received an even poorer interest and besides the use in histology, neither ruthenium ions nor ruthenium compounds have a clear place in medicine and biology. Nevertheless, since the middle seventies, many studies have been published, showing in a convincible and repetitive manner, the possible advantages of ruthenium as a base for new competitive drugs. The aim of this review is therefore that of critically examining the past and the actual work on ruthenium compounds with emphasis on their proposed role in cancer therapy.

Animals↗
PubMed1991

Cancer incidence and geochemical factors in the environment.

Between 1961 and 1987, 9875 cases of cancer were registered in the district of Zdar nad Sazavou in southern Czechoslovakia; this district covers an area of 1627 km2 and has a population of 125,000 living within 197 identifiable communities. The age-standardized cancer incidence (standardized incidence rate, SIR) for selected cancers was calculated for each of the 197 communities. Five distinct geological areas were identified in the district; the percentages of the communities with a high incidence of cancer in each of these five areas were compared and statistically tested. More than 95% of the communities with a significantly high incidence of cancers of the digestive organs, lymphomas, leukaemias and all childhood cancers were situated in the areas containing tectonic faults or geological substrata which allowed radioactive elements (such as U, Rn, Co and Th) and heavy metals (for example, Pb, Zn, Cu and Cd) to intrude to the surface. Important quantities of heavy metals and radioactivity were found in drinking water, air (fall-out, including dust) and aerosols. The role of geochemical factors in the environment as possible causes of the high incidence of some cancers is discussed.

Adult↗
PubMed1990

N-(2,3-dimercaptopropyl)phthalamidic acid (DMPA) increases polonium-210 excretion.

Polonium-210 is one of the most hazardous radionuclides. As recently as 1988, there have been concerns regarding accidental exposures of humans to it. Yet, there have been no studies on the effectiveness of the newer dithiol chelating agents in increasing the excretion of this radioactive heavy metal. In order to accomplish this, a safe and effective method for determining the radioactivity of polonium-210, an alpha emitter, in the feces was developed. The excretion of polonium-210 was studied by giving male Sprague-Dawley rats 210Po (3.33 x 10(7) cpm/kg, intraperitoneal); 1 h later they were given either 5% sodium bicarbonate, N-(2,3-dimercaptopropyl)phthalamidic acid (DMPA) or meso-dimercaptosuccinic acid (DMSA) (0.20 mmol/kg, subcutaneous). Treatment was repeated daily for 12 days. DMPA and DMSA increased the urinary excretion of 210Po, as compared to control animals, 8-fold and 5-fold, respectively. DMPA increased the fecal excretion of 210Po compared to the other treatments and also decreased the level of 210Po in the spleen, a radiosensitive organ. DMPA (0.20 mmol/kg, intravenous) increased biliary levels of 210Po 5-fold compared to controls. The results indicate that DMPA has greater specificity in chelating and increasing the excretion of 210Po than DMSA.

Animals↗
PubMedDate not supplied

New approaches to the study of sphingolipid enriched membrane domains: the use of electron microscopic autoradiography to reveal metabolically tritium labeled sphingolipids in cell cultures.

This paper is the first report on the use of the electron microscopy autoradiography technique to detect metabolically tritium labeled sphingolipids in intact cells in culture. To label cell sphingolipids, human fibroblasts in culture were fed by a 24 hours pulse, repeated 5 times, of 3 x 10(-7) M [1-(3)H]sphingosine. [1-(3)H]sphingosine was efficently taken up by the cells and very rapidly used for the biosynthesis of complex sphingolipids, including neutral glycolipids, gangliosides, ceramide and sphingomyelin. The treatment with [1-(3)H]sphingosine did not induce any morphological alteration of cell structures, and well preserved cells, plasma membranes, and intracellular organelles could be observed by microscopy. Ultrathin sections from metabolic radiolabeled cells were coated with autoradiographic emulsion. One to four weeks of exposition resulted in pictures where the location of radioactive sphingolipids was evidenced by the characteristic appearance of silver grains as irregular coiled ribbons of metallic silver. Radioactive sphingolipids were found at the level of the plasma membranes, on the endoplasmic reticulum and inside of cytoplasmic vesicles. Thus, electron microscopy autoradiography is a very useful technique to study sphingolipid-enriched membrane domain organization and biosynthesis.

Autoradiography↗
PubMed2000

Monoclonal antibody-dendrimer conjugates enable radiolabeling of antibody with markedly high specific activity with minimal loss of immunoreactivity.

For the purpose of radioimmunotherapy, labelling of monoclonal antibody with high specific activity is often necessary, especially when using a radionuclide with a shorter half-life. Polyamine dendrimers (PAMAM) are novel synthetic polymeric molecules with large numbers of amine residues on their spherical surface. In order to bind large numbers of radiometals to single antibody molecules, the generation-4 PAMAM (G4), which has 64 amines, was conjugated with 43 molecules of 2-(p-isothiocyanatobenzyl)-6-methyl-diethylene triamine penta-acetic acid (1B4M), a derivative of DTPA. This product [G4-(1B4M)43] was then conjugated with OST7, a murine monoclonal IgG1. We evaluated the achievable specific activity for 111In labeling, immunoreactivity, biodistribution, and tumor targeting in mice of the 111In- or 153Gd-OST7-G4-(1B4M)43 as compared with radiolabeled OST7-1B4M or 56C-1B4M. The maximum specific activity of 111In-OST7-G4-(1B4M)43 and 111In-OST7-1B4M was 470 and 8.7 GBq/mg (12,700 and 263 mCi/mg), respectively. Immunoreactivity of radiolabeled OST7-G4-(1B4M)43 and OST7-1B4M, as determined by the binding to KT005 cells expressing the antigen, was respectively 91% and 84% of that of 125I-labelled OST7. Biodistribution studies for preparations with maximum specific activity in normal mice 3 h after injection showed that 111In- or 153Gd-OST7-G4-(1B4M)43 cleared faster from the blood and accumulated more in the liver than did 111In- or 153Gd-OST7-1B4M. The dendrimer 1B4M [G4-(1B4M)64] itself showed similar saturation effects with metals. The radioactivity in all the other organs reflected the rapid clearance of radioactivity from the blood. 153Gd-OST7-G4-(1B4M)43 showed specific accumulation in the KT005 tumor. In conclusion, we could successfully bind 49 times as many metal atoms to an antibody molecule as is possible with conventional metal labeling for indium and gadolinium, and did so with minimal loss of immunoreactivity. When we achieved radiolabeling with maximum specific activity, Gd conjugate showed better biodistribution than In conjugate.

Animals↗
PubMed1985

[Rapid analysis of transferrin-iron complexes by isoelectric focusing and radioactive densitometry on gel].

The analysis of the molecular forms of transferrin-iron complexes with 59Fe, was carried out using an isoelectric focusing method on commercially available polyacrylamide plates (PAG plates pH = 4-6,5, LKB). Depending upon the saturation degree of proteins with iron, apotransferrin (pI = 6,1), transferrin-Fe3+ (pI = 5,8), transferrin-2 Fe3+ (a) (pI = 5,5) and transferrin-2 Fe3+ (b) (pI = 5,3) were put forward. When the protein was saturated with iron, a double band was observed which was assigned to the microheterogeneity of the protein and depends upon the sialic content. The quantitative analysis was carried out by studying 59Fe radioactivity distribution directly on the plate. As a control, a specific staining of proteins was achieved. The interpretation of the results is difficult if such a method is used, as some bands are not attributed. Through an unspecific staining, the UV-visible densitometry is not satisfactory enough. The proposed method allows a fast analysis of transferrin-metal complexes labeled with radioactive metals. Such a method would be adaptable to the study of other complexes as transferrin-67Ga, transferrin 111In in order to determine the binding site of metal on the protein and its metal content.

Densitometry↗
PubMed1978

Turnover of metallothioneins in rat liver.

Two electrophoretically distinguishable metallothioneins were isolated from the livers of Cd2+-treated rats and had thiol group/metal ratios of 3:1, a total metal content, in each of these proteins, of 3.6 atoms of Cd2+ + 2.4 atoms of Zn2+/molecule and 4.2 atoms of Cd2+ + 2.8 atoms of Zn2+/molecule and respective apoprotein mol.wts. of 5844 and 6251. Studies with 1 h pulse labels of [3H]cysteine, given after a single injection of ZnCl2 or CdCl2, showed that these metals stimulated radioactive isotope incorporation into the metallothioneins over the control value by 10- and 15-fold respectively. This stimulation was maximal at 4 h after a single CdCl2 injection and decreased to control values by 16 h, suggesting that either a translational event is responding to free intracellular Cd2+ or a short-lived mRNA is being produced or stabilized in response to the metal treatment. In rats chronically exposed to CdCl2, the metallothioneins increased to 0.2% of the liver wet weight from a control value of 2--4 mumol/kg of liver, with a maximum rate of accumulation of 2--3 mumol/h per kg of liver. The turnover of these proteins in control animals was 0.3--0.6 mumoles/h per kg of liver, measured by the rate of disappearance of 203Hg2+, which binds irreversibly to the metallothioneins. Pretreatment with CdCl2 completely stopped the rapid 203Hg turnover observed in untreated animals. Unlike CdCl2, treatment with ZnCl2 increased the concentration of metallothioneins to a new steady-state pool, 11 mumole/kg of liver, after 10 h. The increase in the zinc-thionein pool by exposure to ZnCl2 in vivo was determined to be primarily due to a stimulation of metallothionein biosynthesis.

Amino Acids↗
PubMedDate not supplied

[Use of metal salts for radioprotection of plants during radioactive pollution of the territory].

The applying salts of some metals to radionuclide contaminated soddy-podzolic soil in the zone of Chernobyl nuclear power station or the spraying of plants by its solutions are showing the radioprotective effect (salts of iron, zinc, cobalt and manganese) and decreasing the uptake of 90Sr and 137Cs through roots (salts of zinc, manganese, boron, lithium, cobalt and copper).

Chlorides↗
PubMed1989

Aetiology of Balkan nephropathy: a reappraisal after 30 years.

Balkan nephropathy (BN) has been a complete aetiological puzzle for many years. Intense research produced many controversial results, but also helped some clues to be traced. Thus, it became rather obvious that the disease is caused by environmental factors (though it may be, to some extent, genetically controlled). Among live agents, slow viruses are the only (and theoretically very attractive) possible cause of both BN and urothelial tumours, which occur frequently in BN endemic areas. Apart from occasional visualization of virus-like particles, other evidence supporting this hypothesis has been lacking. The role biological products, particularly fungal toxins, needs to be further defined. An excess of any heavy metal or radioactive substance as a cause of BN is very unlikely indeed; however, a deficiency of a bio-essential element could not be ruled out. Many epidemiological data indicate that water might be a transmitter of the agent(s). A wide range of ions and minerals have been incriminated, but up to now most of the studies have provided negative or inconclusive results. Organic compounds in well water have never been sufficiently considered. Another ignored area are unstable and, particularly, photosensitive substances. Fertilizers, pesticides, analgesics, local herbs and teas have no causal relation to BN.

Balkan Nephropathy↗
PubMed2005

Genotoxic and inflammatory effects of depleted uranium particles inhaled by rats.

Depleted uranium (DU) is a radioactive heavy metal coming from the nuclear industry and used in numerous military applications. Uranium inhalation can lead to the development of fibrosis and neoplasia in the lungs. As little is known concerning the molecular processes leading to these pathological effects, some of the events in terms of genotoxicity and inflammation were investigated in rats exposed to DU by inhalation. Our results show that exposure to DU by inhalation resulted in DNA strand breaks in broncho-alveolar lavage (BAL) cells and in increase of inflammatory cytokine expression and production of hydroperoxides in lung tissue suggesting that the DNA damage was in part a consequence of the inflammatory processes and oxidative stress. The effects seemed to be linked to the doses, were independent of the solubility of uranium compounds and correlating with the type of inhalation. Repeated inhalations seemed to induce an effect of potentiation in BAL cells and also in kidney cells. Comet assay in neutral conditions revealed that DNA damage in BAL cells was composed partly by double strands breaks suggesting that radiation could contribute to DU genotoxic effects in vivo. All these in vivo results contribute to a better understanding of the pathological effect of DU inhalation.

Animals↗
PubMed1997

Health impacts of large releases of radionuclides. Roles of micro-organisms in the environmental fate of radionuclides.

Micro-organisms play important roles in the environmental fate of radionuclides in both aquatic and terrestrial ecosystems, with a multiplicity of physico-chemical and biological mechanisms effecting changes in mobility and speciation. Physico-chemical mechanisms of removal, which may be encompassed by the general term 'biosorption', include adsorption, ion exchange and entrapment. These are features of living and dead organisms as well as their derived products. In living cells biosorptive processes can be directly and indirectly influenced by metabolism, and may be reversible and affected by changing environmental conditions. Metabolism-dependent mechanisms of radionuclide immobilization include metal precipitation as sulfides, sequestration by metal-binding proteins and peptides, and transport and intracellular compartmentation. Chemical transformations of radionuclide species, particularly by reduction, can result in immobilization. Microbial processes involved in solubilization include autotrophic and heterotrophic leaching, complexation by siderophores and other metabolites, and chemical transformations. Such mechanisms are important components of natural biogeochemical cycles for radionuclides and should be considered in any analyses of environmental radionuclide contamination. Several micro-organism-based biotechnologies, e.g. those based on biosorption or precipitation, are of potential use for the treatment of radionuclide contamination.

Adsorption↗
PubMed1994

Comprehensive RNAA of cadmium, cobalt, nickel, and copper using 109Cd, 57Co, and reactor-produced 67Cu as radioisotopic yield monitors.

An existing radiochemical NAA procedure for Cd, Co, and Cu was improved to allow determination of individual radiochemical yields by the radioisotopic tracer technique, thus eliminating errors owing to variable recovery. 109Cd was used as tracer for Cd determination via 115Cd/115mIn, 57Co for Co via 60Co, and potentially for Ni via 58Co, whereas as a novelty 67Cu, produced by reactor irradiation of ZnO of natural isotopic composition (by the 67Zn [n,p] 67Cu reaction) was used for Cu via the indicator nuclide 64Cu. The simple production and purification of 67Cu by anion exchange is described. Results for biological RMs are given and discussed.

Animals↗