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PubMedDate not supplied

Biochemical mechanisms and morphological selectivity in hepatotoxicity: studies in cultures of hepatic-parenchymal and non-parenchymal cells.

Primary cultures of rat-liver parenchymal and non-parenchymal cells have been used to study some of the factors influencing the selective injury that can be caused in vivo by the direct-acting hepatotoxins beryllium, cadmium, ricin and modeccin to either liver-parenchymal or non-parenchymal cells. The studies on beryllium and cadmium compounds show that it is necessary to consider the chemical species generated in the culture medium, since particulate or colloidal forms are taken up predominantly by non-parenchymal cells whereas soluble forms more readily enter parenchymal cells. The studies with the glycoproteins ricin and modeccin illustrate the importance in their selective cell toxicity of specific membrane-recognition processes present in liver cells, particularly uptake in non-parenchymal cells through interactions with terminal mannose oligosaccharides in the toxins.

Animals↗
PubMed1999

Overexpression of the regulatory subunit of gamma-glutamylcysteine synthetase in HeLa cells increases gamma-glutamylcysteine synthetase activity and confers drug resistance.

gamma-Glutamylcysteine synthetase (GCS) is reported to catalyse the rate-limiting step in glutathione biosynthesis, and is a heterodimer composed of a catalytic subunit [heavy subunit (GCSh) of Mr 73000] and a regulatory subunit [light subunit (GCSl) of Mr 31000]. In the present study, we have demonstrated for the first time a potential role for GCSl in resistance towards doxorubicin and cadmium chloride. Addition of recombinant GCSl to HeLa cell extracts in vitro was found to result in an increase in GCS activity of between 2- and 3-fold. Transient transfections of COS-1 cells with the GCSl cDNA cause an increase in GCS activity of approx. 2-fold, and a small but significant (P=0.008) increase in glutathione levels from 126.9+/-4. 2 nmol/mg protein to 178.8+/-19.1 nmol/mg protein. We proceeded to make a HeLa cell line (LN73), which stably overexpresses GCSl. These cells overexpress GCSl approx. 20-fold above basal levels. LN73 was found to have a 2-fold increase in GCS activity (437.3+/-85.2 pmol/min per mg) relative to the control cell line, HL9 (213.4+/-71. 8 pmol/min per mg). In contrast with the transient transfections in COS-1 cells, stable overexpression of GCSl was found not to be associated with an increase in glutathione content. However, when the LN73 and HL9 cells were treated with the glutathione-depleting agent, diethylmaleate, the LN73 cells were found to have an enhanced ability to regenerate glutathione, compared with HL9 cells. The cell lines were treated with various anti-cancer drugs, and their cytotoxicity was examined. No obvious differences in toxicity were observed between the different cell lines following treatment with cisplatin and melphalan. The redox-cycling agent doxorubicin, however, was found to be more toxic (approx. 2-fold) to the HL9 cells than the LN73 cells. When the cells were treated with the carcinogenic transition-metal compound, cadmium chloride, LN73 cells were found to be approx. 3-fold more resistant than HL9 cells.

Animals↗
PubMed1987

Occupational exposure to lead and blood pressure: a study in 105 workers.

A group of workers, occupationally exposed to lead and cadmium compounds (n = 53), was compared to a group of workers not exposed to these metals (n = 52). The average values of systolic, diastolic, and mean blood pressure were found to be higher in the exposed group (p less than 0.05). In contrast with the correlation between CdU and blood pressure, the correlation between PbB and systolic and mean blood pressure remained statistically significant after controlling for age and pulse rate (r = 0.22, p less than 0.05). The prevalence of potential hypertension (defined as systolic blood pressure greater than or equal to 160 mm Hg and/or diastolic blood pressure greater than or equal to 95 mm Hg and/or under treatment for hypertension) was higher in the exposed group, but the observed relative risk was not statistically significant: relative risk = 1.91 (95% confidence limits, 0.90-4.05). Furthermore, a significant correlation between PbB and Hgb (r = -0.28, p = 0.004) was observed. Differences in kidney function, as assessed in this study, were not detected.

Adult↗
PubMed1997

Survival of larvae of Nippostrongylus brasiliensis (nematoda) in solutions of toxic substances.

The aim of this study was to determine the action of zinc, copper, lead and cadmium compounds upon N. brasiliensis invasive nematode larvae. The tested larvae were kept in ZnCl2, CuCl2, Pb(NO3)2 and CdCl2 solutions. The concentrations of toxic substances applied for the study corresponded with level of environmental pollution. All toxins reduced life-space of larvae. In control group they survived about 69 days. In solutions of the Zn, contaminated with 10, 50, 100 and 200 ppm of toxic substance, they survived 42, 16, 14 days and 72 hours. In solution of Cu, contaminated with 5, 10, 50 and 200 ppm of toxin, life--space was reduced to 51, 21, 7 days and 54 hours, respectively. Lead reduced live--space of larvae to 26 days already at the low concentration of 10 ppm and in all higher concentrations (20, 50 and 200 ppm) their survival changed insignificantly (to 22 days). In solution of Cd, contaminated with 0.1 and 0.3 ppm larvae died after 39 and 17 days, respectively, while at higher concentrations of this toxin (3 and 10 ppm) larvae survived only 54 and 30 hours, respectively.

Animals↗
PubMed1992

Plasmid mediated metal and antibiotic resistance in marine Pseudomonas.

Pseudomonas sp isolated from the Bay of Bengal (Madras coast) contained a single large plasmid (pMR1) of 146 kb. Plasmid curing was not successful with mitomycin C, sodium dodecyl sulfate, acridine orange, nalidixic acid or heat. Transfer of mercury resistance from marine Pseudomonas to Escherichia coli occurred during mixed culture incubation in liquid broth at 10(-4) to 10(-5) ml(-1). However, transconjugants lacked the plasmid pMR1 and lost their ability to resist mercury. Transformation of pMR1 into E. coli competent cells was successful; however, the efficiency of transformation (1.49 x 10(2)Hgr transformants microsgm-1 pMR1 DNA) was low. E. coli transformants containing the plasmid pMR1 conferred inducible resistance to mercury, arsenic and cadmium compounds similar to the parental strain, but with increased expression. The mercury resistant transformants exhibited mercury volatilization activity. A correlation existed between metal and antibiotic resistance in the plasmid pMR1.

DNA, Bacterial↗
PubMed1998

Glutathione modifies the toxicity of triethyltin and trimethyltin in C6 glioma cells.

It has been demonstrated that exposure to mercury or cadmium compounds causes alterations in the glutathione system in a model glial cell line, C6. Here we report that two organic tin compounds, triethyltin (TET) and trimethyltin (TMT), are also toxic to these cells with EC50 values for cell death of c. 0.02 microM and 0.8 microM respectively. Exposure for 24 h to either of these compounds at sub-toxic concentrations caused increases in the amount of reduced glutathione (GSH) per cell. Increases in glutathione-S-transferase enzyme activity were also demonstrated after TET or TMT exposure. This suggests that glutathione increases occur in glial cells after toxic insults below that required to cause cell death, possibly acting as a protective mechanism. To test whether GSH plays a role in organotin-induced cell death we manipulated GSH in the culture media or via intracellular GSH and looked at the effects on sensitivity to TET or TMT toxicity. Adding GSH to the culture media did not protect the cells. Depletion of intracellular GSH with buthionine-[S,R] sulphoximine did not alter cytotoxicity of TET or TMT. However, pre-treatment with (-)-2-oxo-4-thiazolidine carboxylic acid (OTC), which increases intracellular GSH levels, protected the cells against both compounds. The EC50 for TMT was increased from 0.77 to 1.8 microM, a 2.3-fold shift, whereas the EC50 for TET was increased > 20-fold, from 0.022 to 0.47 microM. One interpretation of these results is that GSH protects cells against the toxicity of organic tin compounds without reacting directly with them to any significant extent. Under conditions where GSH is depleted, additional protective mechanisms may be active.

Animals↗
PubMed1990

Distribution, localization, and pulmonary effects of yttrium chloride following intratracheal instillation into the rat.

Metabolic behavior and pulmonary toxicity of yttrium chloride (YCl3) deposited in the lung was investigated. Yttrium chloride was instilled intratracheally into rats and the time-course and dose-related changes in distribution of Y between lung tissue and bronchoalveolar lavage fluid (BALF) and pulmonary inflammatory responses were investigated. Pulmonary clearance of Y was very slow and the half-life was estimated to be 168 days. Yttrium content in the supernatant of BALF did not exceed 5 micrograms Y/lung even when a dose of 200 micrograms Y/rat was administered, suggesting that the alveolar surface fluid could retain at most 5 micrograms Y. On the other hand, Y content in the pellet of BALF changed with the number of macrophages retrieved in BALF in both time-course and dose-response experiments. Transmission electron microscopy and X-ray microanalysis suggested that Y was localized in lysosomes of alveolar and interstitial macrophages, and basement membranes. These results clearly explain the long pulmonary half-life of Y. beta-Glucuronidase activity and calcium and phosphorous contents in the supernatant of BALF increased significantly even at the lowest dose (10 micrograms Y/rat). Comparative dose-effect profiles of lactate dehydrogenase activity in BALF supernatant revealed that 1 mol of YCl3 is equivalent to about one-third mole of cadmium compounds and about 3 mol of zinc oxide in the potency for acute pulmonary toxicity.

Animals↗
PubMed2003

Contaminant exposure and effects in pinnipeds: implications for Steller sea lion declines in Alaska.

After nearly 3 decades of decline, the western stock of Steller sea lions (SSL; Eumetopias jubatus) was listed as an endangered species in 1997. While the cause of the decline in the 1970s and 1980s has been attributed to nutritional stress, recent declines are unexplained and may result from other factors including the presence of environmental contaminants. SSL tissues show accumulation of butyltins, mercury, PCBs, DDTs, chlordanes and hexachlorobenzene. SSL habitats and prey are contaminated with additional chemicals including mirex, endrin, dieldrin, hexachlorocyclohexanes, tetrachlorodibenzo-p-dioxin (TCDD) and related compounds, cadmium and lead. In addition, many SSL haulouts and rookeries are located near other hazards including radioactivity, solvents, ordnance and chemical weapon dumps. PCB and DDT concentrations measured in a few SSL during the 1980s were the highest recorded for any Alaskan pinniped. Some contaminant exposures in SSL appear to be elevated in the Gulf of Alaska and Bering Sea compared to southeast Alaska, but there are insufficient data to evaluate geospatial relationships with any certainty. Based on very limited blubber data, current levels of PCBs may not pose a risk to SSL based on comparison to immunotoxicity tissue benchmarks, but SSL may have been at risk from pre-1990 PCB exposures. While exposure to PCBs and DDTs may be declining, SSL are likely exposed to a multitude of other contaminants that have not been monitored. The impacts of these exposures on SSL remain unknown because causal effects have not been established. Field studies with SSL have been limited in scope and have not yet linked contaminant exposures to adverse animal health or population effects. Several biomarkers may prove useful for monitoring exposure and additional research is needed to evaluate their utility in SSL. We conclude that there are insufficient data to reject the hypothesis that contaminants play a role in the continued decline of SSL, and suggest that a coordinated monitoring program be developed which can be related to key biological, ecological and laboratory toxicity data.

Adipose Tissue↗
PubMed2002

Cytochrome P4501A responses in two tropical fish species, riverine catfish (Rita rita) and marine mudfish (Apocryptes bato).

The present study focuses on the establishment of methods for biomarker studies in freshwater and marine fish species as a basis for monitoring the extent of contamination of fisheries resources in tropical waters. Riverine catfish (Rita rita) and marine mudfish (Apocryptes bato) were given a single intraperitoneal injection with two selected inducing compounds; beta-naphthoflavone (BNF, 50 mg/kg) and a polychlorinated biphenyl mixture (Clophen A50, 20 mg/kg), and the heavy metal compound cadmium chloride (CdCl2, 1 mg/kg). Effects on cytochrome P4501A (CYP1A) were determined in post-mitochondrial supernatants (PMS) of liver at days 3 and 10 after treatment. EROD (7-ethoxyresorufin O-deethylase) activity and CYP1A protein level by indirect non-competitive enzyme-linked immunosorbent assay (ELISA) and Western blotting using a monoclonal antibody against fish CYP1A, were measured. BNF and Clophen A50 resulted in induction upto 9.5- and 5-fold, respectively, of CYP1A protein compared to control, while CdCl2 showed significant inhibition in these species. The present study examined the phase-I cytochrome P450 monooxygenase activity and response in these two tropical fish species for the first time.

Animals↗
PubMed1996

Geometry and Electronic Structure of CuCl(6)(4-) Polyhedra Doped into (3-Chloroanilinium)(8)[CdCl(6)]Cl(4)-An EPR and Structural Investigation.

The EPR single-crystal and powder spectra of mixed crystals of (3-chloroanilinium)(8)(Cd(1-x)Cu(x)Cl(6))Cl(4) are measured as a function of temperature and x and analyzed with respect to the geometry and bonding properties of the CuCl(6) polyhedra. These undergo strong distortions due to vibronic Jahn-Teller coupling, with the resulting tetragonal elongation being superimposed by a considerable orthorhombic symmetry component induced by a host site strain acting as a compression along the crystallographic a axis. This strain becomes apparent in the cadmium compound (x = 0), whose crystal structure is also reported [a = 8.701(2) Å, b = 13.975(2) Å, c = 14.173(2) Å, alpha = 81.62(1) degrees, beta = 72.92(1) degrees, gamma = 77.57(1) degrees, triclinic P&onemacr;, Z = 1]. A calculation of the ground state potential surface and its vibronic structure nicely reproduces the g values, Cu-Cl spacings, and ligand field data. At high copper concentrations (including x = 1), the CuCl(6) polyhedra are coupled elastically, with the long axes of neighboring polyhedra having perpendicular orientations. The elastic correlation presumably is not of the long-range antiferrodistortive type, however. Above about 55 K, the angular Jahn-Teller distortion component becomes dynamically averaged within the time scale of the EPR experiment, leading to local tetragonally compressed CuCl(6) octahedra.

Journal Article↗
PubMed2005

Size and ligand effects on the electrochemical and spectroelectrochemical responses of CdSe nanocrystals.

The electrochemical properties of CdSe quantum dots with electrochemically inactive surface ligands (TOPO) have been investigated in comparison with the analogous nanocrystals containing electrochemically active oligoaniline ligands. The TOPO-capped nanocrystals have been studied in a wide size range (from 3 to 6.5 nm) with the goal to amplify the influence of the quantum confinement effect on the electrochemical response. The determined HOMO and LUMO levels have been found in good agreement with the ones obtained from photoluminescence studies and those predicted theoretically. Ligand exchange with aniline tetramer significantly influences the voltammetric peaks associated with the HOMO oxidation and the LUMO reduction of the quantum dots, which are shifted to higher and lower potentials, respectively. These shifts are interpreted in terms of the positive ligand charging which precedes the oxidation of the nanocrystals and the insulating nature of the ligand in the case of the nanocrystal reduction. The ligand-nanocrystal interactions have also been studied by UV-Vis-NIR and Raman spectroelectrochemistry in comparison with a specially prepared model compound which, apart from the anchoring function is identical to the grafted oligoaniline ligand. Both spectroelectrochemical techniques clearly indicate the same nature of the oxidation/reduction pathway for both the model compound and the grafted ligand. The influence of the grafting is manifested by a shift in the onset of the ligand oxidation as compared to the case of the "free" model compound. Since both components (ligands and nanocrystals) mutually influence their electrochemical and spectroelectrochemical properties, the newly developed system can be considered as a true molecular hybrid. Such hybrids are of interest because the potential zone of the ligand electroactivity is well separated from that of the nanocrystals and, as a result, the organic part can be electrochemically switched between the semiconducting and the conducting states with no change in the oxidation state of the nanocrystal. The newly developed system offers therefore the possibility of an electrical addressing of individual nanocrystals via the conducting ligands.

Aniline Compounds↗
PubMed2003

[Recreational drugs and environmental contaminants in mother 's milk].

In Germany and many other countries breast milk contamination in particular with persistent organochlorines and lead declined substantially by 50-70% or more during the last decade. Generally also mercury compounds, cadmium and other environmental contaminants do not pose a toxic threat to the fully breast fed infant, which, according to the current knowledge, could outweigh the advantages of breast-feeding. Industrial regions, large cities and frequent consumption of contaminated fish are factors still positively correlated with elevated breast milk contamination. However, recent study results do not support routine measurement of milk contaminants for decision making on prolonged breast-feeding (more than 4-6 months). Exposure to recreational drugs including tobacco smoking and alcohol drinking is preventable. In case of ongoing abuse decisions on breast-feeding restrictions must be taken individually.

Breast Feeding↗
PubMedDate not supplied

Prevalence of hypertension among cadmium-exposed workers.

In a retrospective study of 311 male workers in an alkaline battery factory, the relationship between exposure to cadmium oxide and hypertension has been investigated. Blood pressure measurements, taken by the same physician, were available for a 30-yr period. When age-matched groups of hypertensive and normotensive workers were compared, employment time was significantly longer (P = .0109) in the hypertensive group. This indicates a possible relationship between exposure to cadmium oxide and the development of hypertension.

Adult↗
PubMed2002

Influence of prior Cd(2+) exposure on the uptake of Cd(2+) and other elements in the phytochelatin-deficient mutant, cad1-3, of Arabidopsis thaliana.

In order to test the potential effect of prior exposure to different Cd concentrations on Cd uptake and accumulation, plants of Arabidopsis thaliana, including a phytochelatin-deficient mutant, cad1-3, and the wild type, were compared. For Cd uptake experiments, plants were grown for 1 week in nutrient solution containing different Cd concentrations (0, 0.05, 0.1, 0.25, 0.5, and 1.0 microM Cd(NO(3))(2)). Thereafter they were subjected to 0.5 microM Cd labelled with (109)Cd for 2 h. Uptake experiments with (109)Cd showed that the phytochelatin-deficient mutant cad1-3, accumulated less Cd than the wild type. Both a lower proportion and lower total amount of absorbed Cd were translocated to the shoot in cad1-3 plants compared to wild-type plants. Cadmium exposure also influenced the amounts of nutrients found, whereby after exposure to high Cd concentrations (0.5, 1.0 microM) during growth, cad1-3 roots contained less Fe, K, Mg, P, and S compared to roots of the wild type. In cad1-3 these elements decreased with increasing Cd concentration. The total Cd content in roots and shoots increased significantly with increasing Cd concentration during growth, although the increase was much less in cad1-3 plants. In time-dependent experiments of Cd uptake carried out between 15 and 120 min on plants not previously exposed to Cd, no significant difference in Cd accumulation between the mutant and wild type were found, although a smaller amount of Cd was translocated to the shoot in cad1-3 plants. The possibility that the differences in Cd accumulation in mutant and wild-type lines may be due to the cytosolic Cd regulation, which is inhibited by the complexation of Cd by phytochelatins, is discussed.

Arabidopsis↗
PubMed1994

Occupational risk factors for bladder cancer: results from a case-control study in Montreal, Quebec, Canada.

A population-based case-control study of the associations between various cancers and occupational exposures was carried out in Montreal, Quebec, Canada. Between 1979 and 1986, 484 persons with pathologically confirmed cases of bladder cancer and 1,879 controls with cancers at other sites were interviewed, as was a series of 533 population controls. The job histories of these subjects were evaluated by a team of chemist/hygienists for evidence of exposure to a list of 294 workplace chemicals, and information on relevant non-occupational confounders was obtained. On the basis of results of preliminary analyses and literature review, 19 occupations, 11 industries, and 23 substances were selected for in-depth multivariate analysis. Logistic regression analyses were carried out to estimate the odds ratio between each of these occupational circumstances and bladder cancer. There was weak evidence that the following substances may be risk factors for bladder cancer: natural gas combustion products, aromatic amines, cadmium compounds, photographic products, acrylic fibers, polyethylene, titanium dioxide, and chlorine. Among the substances evaluated which showed no evidence of an association were benzo(a)pyrene, leather dust, and formaldehyde. Several occupations and industries were associated with bladder cancer, including motor vehicle drivers and textile dyers.

Adult↗