Tuesday, January 15, 2013

Genetic and Epigenetic Mechanisms in metal carcinogenesis (4 of x in a series)

Part One in the series can be found here: http://www.mydepuyhiprecall.com/2013/01/genetic-and-epigenetic-mechanisms-in.html

Part Two   can be found here:http://www.mydepuyhiprecall.com/2013/01/genetic-and-epigenetic-mechanisms-in_7.html

Part Three: chromium 6 metabolism and DNA Damage:http://www.mydepuyhiprecall.com/2013/01/genetic-and-epigenetic-mechanisms-in_8.html

Part Four:  Chromium (Cr)-DNA Adducts

(Just wanted to remind the readers that I am neither  a chemist, doctor nor scientist. Like you, I am trying to make sense of the  literature on systemic issues surrounding the Cr and Co.

What is an adduct?  An adduct (from the Latin adductus, "drawn toward") is a product of a direct addition of two or more distinct molecules, resulting in a single reaction product containing all atoms of all components.[1] The resultant is considered a distinct molecular species. Examples include the adduct between hydrogen peroxide and sodium carbonate to give sodium percarbonate, and the addition of sodium bisulfite to an aldehyde to give a sulfonate.

What do these adducts do? They induce genetic leisons in mammalian cells  and are responsible  for all mutagenic damage generated during Cr 6 reduction to Cr 3. Most of these adducts are only weakly mutegenic*. The predominant form of Cr DNA complexes in cells are ternary adducts which include Cr 3 binding molecules.  Ternary adducts are formed through an attack of DNA by preformed Cr3 complexes and can also be generated in the direct reaction of NEWLY FORMED CR 3 WITH DNA. 

(*In genetics, a mutagen (Latin, literally origin of change) is a physical or chemical agent that changes the genetic material, usually DNA, of an organism and thus increases the frequency of mutations above the natural background level. As many mutations cause cancer, mutagens are therefore also likely to be carcinogens.)

 Looks like this author is questioning whether  the single strand DNA breaks are in fact a result of the Cr or were artifacts of the alkaline assay conditions. [This is an interesting observation.]

So what I can gather from this part of the article  is that oxidative damage is not the only cause of carcinogenesis from the reduction of Cr 6 to Cr 3. 

The final two parts will look at genomic instability, toxicity and Cr 6 carcinogenesis and then Cr as a co-carcinogen which is net new information to me.

The crux of all of this hip issue with Cr 6 vs 3 has to do with the damage that occurs during this reduction of 3 to 6.  While the reduction is  fast, it is apparent that this is where the problem with these metals seem to start, from a cancer perspective anyway.

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