Cadmium mimicks oestradiol in BC.
An argument for getting supermarkets to set up battery collection points. I think high performance batteries have it in. Maybe somebody could clarify.
Thanks
RB
http://www.ncbi.nlm.nih.gov/entrez/q..._uids=10770491
1: Mol Endocrinol. 2000 Apr;14(4):545-53.Click here to read Links
Activation of estrogen receptor-alpha by the heavy metal
cadmium.
* Stoica A,
* Katzenellenbogen BS,
* Martin MB.
Department of Biochemistry and Molecular Biology, Vincent T. Lombardi Cancer Center, Georgetown University, Washington, DC 20007, USA.
Previous studies from this laboratory have shown that the heavy metal
cadmium (Cd) mimics the effects of estradiol in estrogen-responsive breast cancer cell lines. To understand the mechanism by which
cadmium activates estrogen receptor-alpha (ER-alpha), the ability of
cadmium to bind to and activate wild-type and various mutants of ER-alpha was examined. When tested in transient cotransfection assays in COS-1 cells,
cadmium concentrations as low as 10(-11) M activated ER-alpha. Scatchard analysis employing either purified human recombinant ER-alpha or extracts from ER-containing MCF-7 cells demonstrated that l09Cd binds to the ER with an equilibrium dissociation constant of approximately 4 to 5 x 10(-10) M.
Cadmium also blocks the binding of estradiol to ER-alpha in a noncompetitive manner (K(i) = 2.96 x 10(-10) M), suggesting that the heavy metal interacts with the hormone-binding domain of the receptor. To study the role of the hormone-binding domain in
cadmium activation, COS-1 cells were transiently cotransfected with GAL-ER, a chimeric receptor containing the DNA-binding domain of the transcription factor GAL4 and the hormone-binding domain of ER-alpha, and a GAL4-responsive reporter gene. Treatment of the transfected cells with either 10(-6) M
cadmium or 10(-9) M estradiol resulted in a 4-fold increase in reporter gene activity. The effect of
cadmium on the chimeric receptor was blocked by the antiestrogen, ICI-164,384, suggesting that
cadmium activates ER-alpha through an interaction with the hormone-binding domain of the receptor. Transfection and binding assays with ER-alpha mutants identified C381, C447, E523, H524, and D538 as possible interaction sites of
cadmium with the hormone-binding domain of ER-alpha.
PMID: 10770491 [PubMed - indexed for MEDLINE]
Related Links
http://www.portfolio.mvm.ed.ac.uk/st...p29/cadtox.htm
METALS AS TOXINS
CADMIUM
Introduction
Cadmium has no essential biological function and is extremely toxic to humans. In chronic exposure, it also accumulates in the body, particularly in the kidneys and the liver 4, 13. These properties, along with its common useage (see below) make
cadmium one of the commonest environmental metal poisonings. Acute poisoning from inhalation of fumes and ingestion of
cadmium salts can also occur and at least one death has been reported from self-poisoning with
cadmium chloride 1.
Sources
Cadmium has a wide variety of sources in the environment and from industry. One source is from ingestion of grown foodstuffs, especially grain and leafy vegetables, which readily absorb
cadmium from the soil. The
cadmium may occur naturally or as a contaminant and the contaminants include sewage sludge, fertilisers, polluted groundwater and mining effluents.
Cadmium may also contaminate fish 8, 13.
Cadmium is also a constituent of alloys, pigments, batteries, metal coatings for example protective coatings on steel, plastics and fertilisers. Occupational exposure may occur from the manufacture of these products and from welding, and smelting of lead, zinc and copper as these occur in mixed ores with
cadmium.
Cadmium is also found in cigarette fumes (0.007 to 0.35 µg per cigarette) and fumes from vehicles. Residential sites may be contaminated by municipal waste or leaks from hazardous waste sites 1, 12, 13.
Toxicology
Humans have a daily intake of
cadmium from ingestion and inhalation which is around 20 to 40 µg per day, but only 5 to 10% of this is absorbed 8. After absorbtion,
cadmium is transported in the blood bound to albumin. It is taken up by the liver, and, due to its similarity to zinc, causes this organ to induce the synthesis of the protein metallotheionin (see Introduction, metallotheionin), to which it binds. The cadmium-metallotheionin complex then becomes transported to the kidneys, and it is filtered at the glomerulus, but is reabsorbed at the proximal tubule 1, 8. Within the renal tubular cells, the cadmium-MT complex becomes degraded by digestive enzymes, which releases the
cadmium. Renal tubular cells deal with the release of this toxic substance by synthesising MT to neutralise it, but eventually the kidneys loose their synthetic capacity for MT. At this point, the
cadmium has accumulated to a high level in the renal tubular cells, and irreversible cell damage occurs 1, 12. As can be seen above, the renal cells do not have an effective elimination pathway for the
cadmium complex, which means that the half life in the kidney is between 15 and 30 years 1, 8.
The toxic effects of
cadmium are due to its inhibition of various enzyme systems. Like similar heavy metals, it is able to inactivate enzymes containing sulphydryl groups and it can also produce uncoupling of oxidative phosphorylation in mitochondria 4.
Cadmium may also compete with other metals such as zinc and selenium for inclusion into metallo-enzymes and it may compete with calcium for binding sites on regulatory proteins such as calmodulin 8.
Clinical effects
The organs most affected by
cadmium exposure are the kidneys and the lungs. As mentioned above,
cadmium poisoning may be acute by ingestion or inhalation or the poisoning may be chronic at lower levels, which can cause kidney damage by the mechanism described above. In chronic exposure,
cadmium accumulates in the body, particularly the kidneys and liver 4, 13.
An acute intake of
cadmium causes testicular damage. Within a few hours of exposure, there is necrosis and degeneration of the testes with complete loss of spermatozoa. This is thought to be due to an effect on the blood supply to these organs, reducing the blood flow 4, 12. If the
cadmium is inhaled, then severe lung irritation and damage (often called ‘fume fever’) occur. The patient displays pleuritic chest pain, dyspnoea, cyanosis, fever and tachycardia, and the pulmonary oedema which occurs may be life-threatening. Constitiutional symptoms also occur such as diarrhoea and malaise 4, 8, 12. Acute ingestion of
cadmium produces severe gastrointestinal irritation, which is manifest as severe nausea and vomiting, abdominal cramps and diarrhoea. A lethal dose of
cadmium for ingestion is estimated to be between 350 and 8900 milligrams 8.
The chronic effects of
cadmium are dose-dependent and also depend on the route by which the metal enters the body. Chronic inhalation causes emphysema and obstructive airways disease, and these occur before kidney damage is seen 1, 8, 12. However, 20 years exposure may be needed before these effects are seen 13. Long term ingestion causes kidney damage, which is first seen as proteinuria and ß2microglobulinuria 8, 13. In prolonged
cadmium exposure, disorders of calcium metabolism occur, causing osteomalacia 4, 8, 13. This leads to painful fractures, hence the name given to the chronic exposure disease in Japan: Itai-itai disease (literally "ouch!-ouch!" disease) 4, 8, 12.
Cadmium is also known to be carcinogenic, and in studies has been linked with cancers in the lungs and prostate 8, 12, 13.
Treatment
At present, there is no effective treatment for
cadmium intoxication, and patients are given supportive treatment according to their symptoms. However, it is thought that some of new chelating agents may be effective (see the Treatment section, particularly "chelating agents") 1.
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