Thursday, January 3, 2013

Genetic and Epigenetic Mechanisms in metal carcinogenesis (1 of x in a series)

Someone referred  me to this article and I found it fascinating.  It is a bit complicated to understand so I am going to run a series on it as I do when I myself have to dissect the information in order to understand the key points.
 
You may look at this and wonder why I would bother with this article.  Simple.  While the Chromium in our body did not arrive there through the water, the chromium that enters your system DOES IN FACT ENTER AS CHROMIUM 6 (THE TOXIC FORM.)  It doesn't stay in its toxic form and in fact is then broken down to Chromium 3.  The items that most interested me were the clear types of damage that is caused by Chromium 6 during the conversion process.
 
Given this journal article is long, it will be a long sequence. I think you will find it very interesting. I learned quite a bit reading it over 4-5 times.
 
 
2008 Jan;21(1):28-44. Epub 2007 Oct 30.

Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: nickel, arsenic, and chromium.

Source

National Cancer Institute, Frederick, MD 21702, USA.

Abstract

Chronic exposure to nickel(II), chromium(VI), or inorganic arsenic (iAs) has long been known to increase cancer incidence among affected individuals. Recent epidemiological studies have found that carcinogenic risks associated with chromate and iAs exposures were substantially higher than previously thought, which led to major revisions of the federal standards regulating ambient and drinking water levels. Genotoxic effects of Cr(VI) and iAs are strongly influenced by their intracellular metabolism, which creates several reactive intermediates and byproducts. Toxic metals are capable of potent and surprisingly selective activation of stress-signaling pathways, which are known to contribute to the development of human cancers. Depending on the metal, ascorbate (vitamin C) has been found to act either as a strong enhancer or suppressor of toxic responses in human cells. In addition to genetic damage via both oxidative and nonoxidative (DNA adducts) mechanisms, metals can also cause significant changes in DNA methylation and histone modifications, leading to epigenetic silencing or reactivation of gene expression. In vitro genotoxicity experiments and recent animal carcinogenicity studies provided strong support for the idea that metals can act as cocarcinogens in combination with nonmetal carcinogens. Cocarcinogenic and comutagenic effects of metals are likely to stem from their ability to interfere with DNA repair processes. Overall, metal carcinogenesis appears to require the formation of specific metal complexes, chromosomal damage, and activation of signal transduction pathways promoting survival and expansion of genetically/epigenetically altered cells.

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