Definition
A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens.
Description
Chromium is a naturally occurring heavy metal found in the environment commonly in trivalent, Cr(III), and hexavalent, Cr(VI), forms. The reduction of Cr(VI) to Cr(III) results in the formation of reactive intermediates that contribute to the cytotoxicity, genotoxicity and carcinogenicity of Cr(VI)-containing compounds. The major non-occupational source of chromium for humans is food such as vegetables, meat, urban air, hip or knee prostheses and cigarettes. Cr(VI) is a widely used in industrial chemicals, extensively used in paints, metal finishes, steel including stainless steel manufacturing, alloy cast irons, chrome and wood treatment. On the contrary, Cr(III) salts such as chromium polynicotinate, chromium chloride and chromium picolinate (CrP) are used as micronutrients and nutritional supplements and have been demonstrated to exhibit a significant number of health benefits in animals and humans. Physiologically, it exists as an ion in the body. Chromium enters the body through the lungs, gastro-intestinal tract and to a lesser extent through skin. Inhalation is the most important route for occupational exposure, whereas non-occupational exposure occurs via ingestion of chromium-containing food and water. Regardless of route of exposure Cr(III) is poorly absorbed whereas Cr(VI) is more readily absorbed. Further, absorption of Cr(VI) is poorer by oral route, it is thus not very toxic when introduced by the oral route. But chromium is very toxic by dermal and inhalation routes and causes lung cancer, nasal irritation, nasal ulcer, hypersensitivity reactions and contact dermatitis. All the ingested Cr(VI) is reduced to Cr(III) before entering in the blood stream. The main routes for the excretion of chromium are via kidney/urine and the bile/feces. Cr(III) is unable to enter into the cells but Cr(VI) enters through membrane anionic transporters. Intracellular Cr(VI) is metabolically reduced to Cr(III). Cr(VI) does not react with macromolecules such as DNA, RNA, proteins and lipids. However, both Cr(III) and the reductional intermediate Cr(V) are capable of co-ordinate, covalent interactions with macromolecules. Chromium is an essential nutrient required by the human body to promote the action of insulin for the utilization of sugars, proteins and fats. CrP has been used as nutritional supplement; it controls blood sugar in diabetes and may reduce cholesterol and blood pressure levels. Chromium increases insulin binding to cells, insulin receptor number and activates insulin receptor kinase leading to increased insulin sensitivity. But high doses of chromium and long term exposure of it can give rise to various, cytotoxic and genotoxic reactions that affect the immune system of the body. However, the mechanism of the Cr(VI)-induced cytotoxicity is not entirely understood. A series of in vitro and in vivo studies have demonstrated that Cr(VI) induces oxidative stress through enhanced production of reactive oxygen species (ROS) leading to genomic DNA damage and oxidative deterioration of lipids and proteins. A cascade of cellular events occur following Cr(VI)-induced oxidative stress including enhanced production of superoxide anion and hydroxyl radicals, increased lipid peroxidation and genomic DNA fragmentation, modulation of intracellular oxidized states, activation of protein kinase C, apoptotic cell death and altered gene expression. Some of the factors in determining the biological outcome of chromium exposure include the bioavailability, solubility of chromium compounds and chemical speciation, intracellular reduction and interaction with DNA. The chromium genotoxicity manifests as several types of DNA lesions, gene mutations and inhibition of macromolecular synthesis. Further, chromium exposure may lead to apoptosis, premature terminal growth arrest or neoplastic transformation. Chromium-induced tumor suppressor gene p53 and oxidative processes are some of the major factors that may determine the cellular outcome. Studies have utilized these approaches to understand the interrelationship between chromium-induced genotoxicity, apoptosis and effects on immune response. (A7701).
Top Gene Interactions
Related Pathways
Chromium Health Effects
- Amphiglycemic
- Anti acne
- Anti advanced glycation end products
- Anti aging
- Anti atherosclerotic
- Anti CFS
- Anti corneotic
- Anti diabetic
- Antidote
- Anti fatigue
- Anti glycosuric
- Anti obesity
- Anti syndrome-X
- Anti triglyceride
- Cardioprotective
- Energizer
- Hypocholesterolemic
- Hypoglycemic
- Hypotensive
- Immunomodulator
- Insulinogenic
- Memorigenic
General Information
- Metabolism:
Chromium is absorbed from oral, inhalation, or dermal exposure and distributes to nearly all tissues, with the highest concentrations found in kidney and liver. Bone is also a major storage site and may contribute to long-term retention. Hexavalent chromium's similarity to sulfate and chromate allows it to be transported into cells via sulfate transport mechanisms. Inside the cell, hexavalent chromium is reduced first to pentavalent chromium, then to trivalent chromium by different pathways including ascorbate, glutathione, and nicotinamide adenine dinucleotide. Chromium is almost entirely excreted in the urine. (A12, L16)
- Uses/Sources:
Elemental chromium is used mainly for making steel. Hexavalent chromium is used for chrome plating, dyes and pigments, leather tanning, and wood preserving. (A12, L17)
- Health Effects: Hexavalent chromium is a known carcinogen. Chronic inhalation especially has been linked to lung cancer. Hexavalent chromium has also been shown to affect reproduction and development. (A12)
- Symptoms:
Breathing hexavalent chromium can cause irritation to the lining of the nose, nose ulcers, runny nose, and breathing problems, such as asthma, cough, shortness of breath, or wheezing. Ingestion of hexavalent chromium causes irritation and ulcers in the stomach and small intestine, as well as anemia. Skin contact can cause skin ulcers. (L16)
- Treatment:
There is no known antidote for chromium poisoning. Exposure is usually handled with symptomatic treatment. (L16)
- Route of Exposure:
Oral (L16) ; inhalation (L16); dermal (L16)
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
DNA | Trivalent chromium may also form complexes with peptides, proteins, and DNA, resulting in DNA-protein crosslinks, DNA strand breaks, DNA-DNA interstrand crosslinks, chromium-DNA adducts, chromosomal aberrations and alterations in cellular signaling pathways. (L16) |
2008 |
Histone deacetylase 1 | Chromium can cause transcriptional repression by cross-linking histone deacetylase 1-DNA methyltransferase 1 complexes to CYP1A1 promoter chromatin, inhibiting histone modification. (A35) |
17682057 |
Mitogen-activated protein kinase 1 Mitogen-activated protein kinase 3 |
Chromium has been shown to induce carcinogenesis by overstimulating cellular regulatory pathways and increasing peroxide levels by activating certain mitogen-activated protein kinases. (A34) |
8616849 |
Metal regulatory transcription factor 1 | Chromium may increase its own toxicity by modifying metal regulatory transcription factor 1, causing the inhibition of zinc-induced metallothionein transcription. (A36) |
18057785 |
DNA | Trivalent chromium may also form complexes with peptides, proteins, and DNA, resulting in DNA-protein crosslinks, DNA strand breaks, DNA-DNA interstrand crosslinks, chromium-DNA adducts, chromosomal aberrations and alterations in cellular signaling pathways. (L16) |
2008 |
Histone deacetylase 1 | Chromium can cause transcriptional repression by cross-linking histone deacetylase 1-DNA methyltransferase 1 complexes to CYP1A1 promoter chromatin, inhibiting histone modification. (A35) |
17682057 |
Mitogen-activated protein kinase 1 Mitogen-activated protein kinase 3 |
Chromium has been shown to induce carcinogenesis by overstimulating cellular regulatory pathways and increasing peroxide levels by activating certain mitogen-activated protein kinases. (A34) |
8616849 |
Metal regulatory transcription factor 1 | Chromium may increase its own toxicity by modifying metal regulatory transcription factor 1, causing the inhibition of zinc-induced metallothionein transcription. (A36) |
18057785 |