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PubMed2006

Characterization and in vitro cytotoxicity testing of ethanolamine-derived cadmium chelating agents.

We have synthesized and characterized the new cadmium chelating agent potassium bis(2-hydroxyethyl)aminoethyldithiocarbonate hemihydrate, K[bhexan] x 0.5H2O (2), that is structurally related to the known effective in vivo cadmium chelating agent potassium bis(2-hydroxyethyl)dithiocarbamate, K[bhedtc] (1). The corresponding cadmium complex of 2 differs from di(bis(2-hydroxyethyl)dithiocarbamato)cadmium(II), Cd(bhedtc)2 (3), in that the insoluble compound exhibits an elemental composition consistent with a cadmium:ligand ratio of 2:1. The cytotoxicity of the 1-3 was investigated using the human osteoblast-like cell line, Saos-2. Compounds 1 or 2 did not affect cell adherence or cell viability in the 100-500 microM concentration range studied, whereas 3 resulted in a concentration-dependent increase in loss of cell adherence and decrease in cell viability. Overall, the results of the loss of cell adherence, trypan blue exclusion and MTT assays showed that administration of 3 (cadmium complex of 1) resulted in cytotoxicity lower than that of cadmium chloride, but higher than that of the chelator 1 alone. The effect of simultaneous addition of cadmium chloride and 1 or 2 on cell viability was also assessed using the MTT assay. For the 100 microM cadmium chloride experiments, cell viability comparable to control cells was achieved for both 1 and 2 in the 100-500 microM concentration range studied. Cell viability comparable to control cells was achieved for 1 but not 2 in the 100-500 microM concentration range studied for the 200 microM cadmium chloride experiments. Thus 1 appears more effective than 2 in the ability to mediate the cytotoxic effects of cadmium in vitro upon concomitant administration.

Cadmium↗
PubMed2006

Effects of cadmium and enhanced UV radiation on the physiology and the concentration of UV-absorbing compounds of the aquatic liverwort Jungermannia exsertifolia subsp. cordifolia.

The aquatic liverwort Jungermannia exsertifolia subsp. cordifolia was cultivated for 15 d under controlled conditions to study the single and combined effects of cadmium and enhanced ultraviolet (UV) radiation. Both cadmium and UV radiation caused chlorophyll degradation and a decrease in the maximum quantum yield of photosystem II (PSII), together with an increase in the mechanisms of non-photochemical dissipation of energy (increase in the xanthophyll index). Cadmium was more stressing than UV radiation, since the metal also influenced photosynthesis globally and caused a decrease in net photosynthetic rates, in the effective quantum yield of photosynthetic energy conversion of PSII, and in the maximal apparent electron transport rate through PSII. Ultraviolet radiation increased the level of trans-p-coumaroylmalic acid and cadmium increased trans-phaselic and feruloylmalic acids. The increase in these compounds was probably related to both a more efficient absorption of harmful UV radiation and an enhanced protection against oxidative stress. DNA damage was specifically caused by UV-B radiation, but was intensified under the presence of cadmium, probably because the metal impairs the DNA enzymatic repair mechanisms. Ultraviolet radiation and cadmium seemed to operate additively on some physiological processes, while other responses were probably due to either factor alone.

Cadmium↗
PubMed1996

Cadmium mobilization by nitrogen donor chelating agents.

The relative abilities of a series of acyclic polyamine chelating agents containing only nitrogen donors (N-donors) to induce the urinary excretion of cadmium has been examined in the rat. The compounds examined include triethylenetetramine dihydrochloride (TRIEN), tris(2-aminoethyl)amine trihydrochloride (TREN), tetraethylenepentamine pentahydrochloride (TETRAEN), and pentaethylenehexamine hexahydrochloride (PENTAEN). Sodium N-methyl-D-glucamine-N-carbodithioate (NaG) was used as a positive control compound. The polyamines induced a significant increase in the urinary excretion of cadmium in rats that had been loaded with cadmium at least 4 d prior to the polyamine treatments. A comparison of these with similar data on macrocylic nitrogen donor systems, which form much more stable complexes with cadmium but are also ineffective in enhancing the excretion of cadmium from such aged deposits, suggests that the factors responsible for the relative inefficiency of these compounds may involve either a difficulty in penetrating cellular membranes or a slow rate of reaction with biologically bound cadmium. The occurrence of oliguria and anuria following the administration of the several of the polyamines indicates that their use is accompanied by significant renal damage in cadmium-exposed rats.

Animals↗
PubMed1997

Comparative studies of in vivo genotoxic effects of cadmium chloride in rat brain, kidney and liver cells.

Cadmium chloride-induced DNA damage was investigated in individual brain, kidney and liver cells isolated from rats gavaged 14 mg/kg/day cadmium chloride. Animals were sacrificed on days 2, 4, 8, 16, and 33, and DNA damage was determined using the recently developed alkaline microgel electrophoresis technique. Data for DNA migration from 50 randomly selected cells clearly show significant increases in DNA damage in cells from three different organs of cadmium chloride gavaged animals compared to saline treated control animals (33 day control, brain 64.7 +/- 5.3, kidney 75.5 +/- 9.4, liver 67.9 +/- 5.7 microm; 33 days experimental, brain 284.3 +/- 16.9, kidney 397.9 +/- 11.3, liver 315 +/- 22.5 microm; these values represent length of exposure in days and length of DNA migration in micron). There was an increase in DNA damage for all three cell types, with increasing duration of treatment. Cadmium (CdCl2) induced levels of DNA single strand breaks were more pronounced in kidney cells than in cells from the other two organs. Body and organ weights decreased of treated animals were decreased as compared to control. Results of this study indicate a potential of cadmium to be a genotoxic compound.

Animals↗
PubMed2001

Toxicity, bioaccumulation, and interactive effects of organotin, cadmium, and chromium on Artemia franciscana.

The effects of three organotin compounds-trimethyltin chloride, dimethyltin dichloride, and dibutyltin diacetate-and two heavy metals-cadmium and hexavalent chromium-on Artemia franciscana mortality are investigated in this study. Of all the compounds tested in this work, trimethyltin chloride was, by far, the most toxic. The toxicity order for the five compounds was trimethyltin chloride > potassium dichromate > dimethyltin dichloride > dibutyltin diacetate > cadmium chloride. The big difference in toxicity between dialkyltin and trialkyltin was not accompanied by an equally big difference in bioaccumulation. At a Sn concentration in water of 10 mg/L, the bioconcentration factor was 50 for dimethyltin dichloride and 75 for trimethyltin chloride. At a Sn concentration in water of 100 mg/L, the bioconcentration factor for 6 for dimethyltin dichloride and 9 for trimethyltin chloride. The interactive effect of trimethyltin chloride and cadmium, as well as that of trimethyltin chloride and chromium, was found to be synergistic. Also found to be synergistic was the interactive effect of trimethyltin chloride with cadmium and chromium applied together.

Animals↗
PubMed2006

Composition and production of thiol constituents induced by cadmium in the marine microalga Tetraselmis suecica.

Time course of intracellular levels of different thiols (phytochelatins, desglycyl-phytochelatins, glutathione, gamma-glutamylcysteine [gamma-Glu-Cys], and cysteine) were studied in the microalga Tetraselmis suecica exposed to different cadmium concentrations for 8 d. The cadmium concentrations assayed were 3, 7.9, 15, and 30 mg/L. Contents of thiol compounds synthesized by this microalga changed with cadmium concentration and with time of exposure. Cysteine concentrations increased significantly compared with those of gamma-Glu-Cys and glutathione in cultures containing 7.9, 15, and 30 mg/L. The increase in the amount of glutathione was significant only in cells exposed to the higher cadmium concentrations (15 and 30 mg/L). Nevertheless, in all the cadmium concentrations assayed, gamma-Glu-Cys levels were constant. A rapid increase in phytochelatins was observed with increased cadmium concentration during the first days of culture. The type of phytochelatins (number of subunits) also was dependent on the concentration of cadmium. The rate of (gamma-Glu-Cys)3-Gly accumulation was higher than those of other types of phytochelatins throughout the culture in cells exposed to 3, 15, and 30 mg/L. However, in cultures treated with 7.9 mg/L, (gamma-Glu-Cys)4-Gly increased substantially after 8 d of culture, exceeding the amount of (gamma-Glu-Cys)3-Gly. Cultures exposed to the higher cadmium concentrations (15 and 30 mg/L) showed a decrease in phytochelatins after 4 and 3 d of culture, respectively, whereas an increase in cysteine and glutathione occurred at the same time. A rapid decrease in phytochelatins also was measured when cells were placed into cadmium-free medium. This decrease is consistent with a degradation of the phytochelatins.

Cadmium↗
PubMed1977

Metals as mutagens.

A number of metals are mutagenic in bacteria or phage. These include compounds of arsenic, chromium, copper, iron, manganese, molybdenum, platinum, and selenium. Compounds containing alumium, antimony, arsenic, cadmium, copper, lead, mercury, nickel, and tellium have been shown to induce chromosomal aberrations or abnormal cell divisions in animal or plant cells. Genetic evidence suggests that arsenic, chromium, and molybdenum compounds may influence the accuracy of DNA repair processes in microorganisms.

Animals↗
PubMed1985

[Evaluation of occupational exposure to cadmium based on analysis of air in the work area. II. Cadmium oxide levels in the air of work areas during cadmium production in a non-ferrous metal foundry].

By stationary measurements the levels of cadmium oxide aerosols concentrations in air at particular workplaces related to cadmium production at non-ferrous metals mill have been determined. High concentrations of that compound have been found at such technological operations as unloading of cadmium-bearing raw materials, batching of cadmium sponge in the induction furnace and casting of fused cadmium into moulds. With the personal dosimetry technique, concentrations of that compound in the workers' breathing zone have been determined. Those were within 0.16-1.84 mg/m3, so--above the TLV values. However, those concentrations do not necessarily reflect the occupational exposure magnitude, as the workers had respirators.

Air Pollutants, Occupational↗
PubMed1991

The effect of trithiomolybdate and some selenium compounds upon 109Cd labeled rat metallothionein in vitro: the possibilities for cadmium chelation therapy.

The main binding protein for 109Cd was metallothionein after in vitro incubation of various tissue cytosol preparations obtained from rats supplemented with zinc. The exception was heart cytosol where the label was associated with higher molecular weight proteins. The metallothionein-bound 109Cd was sensitive to trithiomolybdate and moved too higher molecular weight proteins, presumably because of the creation of new stronger ligands by the association of thiomolybdate with these proteins. The 109Cd binding was affected by selenate, selenite, and selenide while molybdate, sulphate, and thiosulphate were ineffective. It is proposed that thiomolybdates should be investigated for use in the therapy of in vivo cadmium toxicity because they can remove the accumulated metal from metallothionein.

Animals↗
PubMed1981

Urinary beta 2 microglobulin in the biological monitoring of cadmium workers.

Urinary beta 2 microglobulin (beta 2m) estimation has been added to an existing pre-employment and periodic medical surveillance programme for cadmium workers. Pre-employment values were measured in 203 men not occupationally exposed to cadmium. The overall geometric mean was 76 microgram/l (adjusted to specific gravity 1016): a significantly higher level of 96 microgram/l was found in the specimens stored continually at -20 degrees C after voiding, compared with 73 microgram/l in specimens that thawed during transport. Sodium azide had been added to all specimen bottles. Employees exposed to cadmium pigments at various stages of their manufacture had no evidence of raised urinary beta 2m despite exposures above 50 microgram/m3 for up to 11 years. This is believed to be due to the insolubility of the compounds. Five known cases of cadmium induced proteinuria whose exposure ceased up to 15 years ago had raised urinary beta 2m concentrations. Moderately raised concentrations were found in seven others with a history of cadmium oxide exposure and in whom proteinuria has never been detected. The place of urinary beta 2m in the health care of cadmium workers is discussed and the question of correct management of a cadmium worker with a high beta 2m is raised.

Adolescent↗
PubMedDate not supplied

Chirality, charge, and chain branching effects on dithiocarbamate-induced mobilization of cadmium from intracellular deposits in mice.

The effects of three major structural features on the intracellular cadmium mobilizing potency of dithiocarbamates have been examined. These features, the chirality of the groups, the total ionic charge of the chelating agent, and the extent of chain branching, would be expected to affect the pharmacological properties of these chelating agents but to have little effect on the stability constants of the cadmium complexes involved. A total of 25 compounds (including 21 new ones) was prepared and used in animal studies designed to evaluate these effects. These included a series of amphipathic dithiocarbamates of the general type R1N(R2)CS2-Na+, where R1 is a relatively nonpolar organic group and R2 is derived from a reducing hexose. All of the factors examined influenced the potency of dithiocarbamates in the mobilization of cadmium from intracellular deposits. The compounds with R2 = galactose or mannose and R1 = benzyl were both more effective than the corresponding glucose derivatives in inducing the removal of cadmium from the liver and the whole body. Increases in the net negative charge of the chelating agent uniformly decreased the observed potency in the mobilization of hepatic and renal cadmium deposits. The replacement of a normal alkyl group by a branched-chain group of the same molecular weight also led to an increase in potency for the two pairs of compounds examined. Dithiocarbamates which are not amphipathic because of the presence of similar polar substituents for both R1 and R2, such as sodium diarabitylamine carbodithioate, were relatively ineffective as agents for the mobilization of intracellular cadmium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Cancer of the brain and nervous system and occupational exposures in Finnish women.

Occupational agents were evaluated for the risk of brain-nervous system cancer in a cohort of 413,877 Finnish women with blue-collar occupations in 1970. Observed and expected numbers of incident cases and the intensities of exposure to 25 agents were generated for 183 job titles from 1971 to 1995. Poisson regression models linked incidence and exposure data. Increased risks were found for medium/high intensities of iron (standardized incidence ratio [SIR], 2.15; 95% confidence interval [CI], 0.96 to 4.80), oil mist (1.95; 0.97 to 3.90), any chromium compounds (1.51; 0.85 to 2.67), electromagnetic fields (1.37; 0.98 to 2.10), aliphatic and alicyclic hydrocarbon compounds (1.34; 0.80 to 2.27), lead (1.27; 0.81 to 2.01), cadmium (1.26; 0.72 to 2.22), and aromatic hydrocarbon compounds (1.20; 0.71 to 2.03). Strengths of the study include fair number of cases, virtually complete case coverage, and a high-quality job exposure matrix. Ecological design and cross-sectional job assessment introduced exposure misclassification and tended to drive risk estimates toward unity.

Brain Neoplasms↗
PubMed1983

Effects of tumor promoters on the frequency of metallothionein I gene amplification in cells exposed to cadmium.

Three potent tumor promoters of different classes, 12-O-tetradecanoylphorbol-13-acetate, dihydroteleocidin B, and aplysiatoxin, and two moderate tumor promoters, mezerein and debromoaplysiatoxin, enhanced the frequency of appearance of cadmium-resistant Chinese hamster lung cells when the cells were exposed to cytotoxic levels of CdCl2. With these compounds, the activity to induce cadmium-resistant cells correlated well with the potency of tumor-promoting activity. Cadmium resistance, which persisted after removal of the tumor promoters, was associated with the overproduction of metallothionein I messenger RNA. The amplified metallothionein I genes were shown by Southern blotting experiments. The relevance of the gene amplification caused by tumor promoters is discussed in relation to cancer development and progression.

Alkaloids↗
PubMed1994

Presentation of a general algorithm to include effect assessment on secondary poisoning in the derivation of environmental quality criteria. 2. Terrestrial food chains.

In a previous study a simple algorithm was presented for effect assessment on secondary poisoning of birds and mammals. This algorithm (MPC = NOECfish-eater/BCFfish) was drawn up by analyzing a two-step aquatic food chain (water-fish-bird/mammal). The algorithm was used to test whether quality criteria set for surface water, based on effect assessment for aquatic organisms, constitute a "safe" level for secondary poisoning. The present study analyzes whether this algorithm can equally well be used for effect assessment in a terrestrial food chain. The pathway soil-earthworm-bird/mammal was used as an example for a terrestrial food chain. Literature data of six selected compounds (lindane, dieldrin, DDT, PCP, cadmium, and mercury) on both bioconcentration factors for earthworms and toxicity data for birds and mammals were studied. Important differences were found between BCFs for this terrestrial pathway and BCFs for the aquatic pathway analyzed in the previous study. It was found that BCFs for earthworms were more dependent on soil-related properties than on compound-specific properties. Hence, it was concluded that the algorithm MPC = NOECworm-eater/BCFworm can be used only for effect assessment on terrestrial food chain in defined situations. By calculating maximum permissible concentrations for secondary poisoning (MPCsp) for a standard soil situation and comparing these to MPCs for soil organisms, it was concluded that secondary poisoning could be a critical pathway for cadmium and methyl mercury. For methyl mercury secondary poisoning in an aquatic food chain was also a critical pathway. Secondary poisoning of fish-eating birds and mammals is not likely to occur for cadmium at concentrations in water below the MPC calculated for aquatic organisms.

Algorithms↗
PubMed1984

Sodium N-methyl-D-glucamine dithiocarbamate and cadmium intoxication.

The sodium and ammonium salts of N-methyl-D-glucamine dithiocarbamate were prepared and their usefulness as antidotes for cadmium intoxication investigated. This chelating agent was found to be effective in both acute and repeated exposure cadmium poisoning. A single intraperitoneal injection of sodium N-methyl-D-glucamine dithiocarbamate (NaNMG-DTC), administered at a level greater than 1.1 mmol/kg body weight, protects against a normally lethal (greater than 95%) dose of cadmium chloride (10 mg CdCl2/kg body weight) and results in a subsequent dose-dependent decrease in the liver and kidney burdens of cadmium ion. In repeated exposure cadmium intoxication, repeated administration of NaNMG-DTC can result in substantial reductions in both the kidney (71%) and the liver (40%) levels of cadmium. The LD50 of the compound was not determined, but single injections of 26.6 mmol/kg body weight (injectate volume 1.0 ml) are well tolerated in mice.

Animals↗
PubMed1986

Comparative antidotal effects of diethyldithiocarbamate, dimercaptosuccinate, and diethylenetriaminepentaacetate against cadmium-induced testicular toxicity in mice.

The compounds diethyldithiocarbamate (DDTC, Dithiocarb), 2,3-dimercaptosuccinic acid (DMSA), and diethylenetriaminepentaacetic acid (DTPA) were evaluated for effectiveness in protecting mouse testes following administration of an LD100 dose of CdCl2 X 2.5 H2O (Cd). Toxicologic responses were assessed by light microscopic techniques. DTPA gave the most effective testicular protection of the three compounds when given within 30 minutes prior to Cd, but only DDTC was effective when given 30 minutes or longer after Cd. Degenerative changes were minimal when DDTC was given as late as three hours after Cd, and were mild following a four-hour interval. However, the changes were marked, but less severe than in mice receiving Cd only, when DDTC was administered five hours after Cd.

Animals↗
PubMed2000

Synergistic effect of vitamin C on DNA damage induced by cadmium.

Salts of divalent cadmium are well-known human mutagens and carcinogens. In the present work, the ability of vitamin C to modulate genotoxic effects of cadmium chloride on human lymphocytes was assessed using single cell gel electrophoresis (comet assay). Vitamin C at 20 and 100 micromol/l and cadmium at 5, 30 and 150 micromol/l significantly increased the tail moment of lymphocytes. Vitamin C also increased the tail moment of cells exposed to cadmium. This effect was concentration-dependent: the higher the vitamin C concentration the greater the tail moment. The combined effects of cadmium and vitamin C were more pronounced at all concentrations tested than the sum of the effects of the compounds applied separately (p < 0.05), so cadmium and vitamin C can be considered to have synergistic effects. The results obtained can be partly explained by the participation of cadmium in the Fenton reaction and reduction of its oxidized form by vitamin C.

Ascorbic Acid↗