Sunday, July 31, 2011

Chromium 3 results in permanent modification to DNA in MoM hip? (2 of 6.) What does this mean?

  I would like to understand what it means when they say that "direct binding of Cr3 to DNA is well documented" and why this matters to us as patients.

  • Wolf et al 1989
  • Landon et al 2004
  • Bacon et al 1983
  • Martnett 1999
  • Hartwig et al 2003
I will explore this in a series of 6 posts, this being post two  which is a brief review of post 8 Review of the Cell biology surrounding metal on metal hips (8 of x in a series) .

First, I wanted to mention that the Depuy hip contains Chromium 3.  It is my understanding that the Chromium 3 is not oxidized from Chromium 6.  I will double check on that because I have been repeatedly told that Chromium 3 is a non carcinogen while Chromium 6 is a carcinogen.

The most common forms of chromium are trivalent (chromium 3) and hexavalent (chromium 6); in its trivalent state, the chromium atom is missing three electrons, and in its hexavalent state, it is missing six electrons. In the environment, chromium usually exists in the trivalent form. It is possible for one form to change into the other when chemical conditions are right. Although the trivalent form of chromium shows very low toxicity, both the federal and California EPA have designated hexavalent chromium a carcinogen. (http://www.chromium6.org/)

There is substantial evidence from laboratory studies that chromium 6 can damage DNA and is a mutagen.

Since the prolonged exposure to chromium results in, allowing the chromium 6 to get accumulate in the cells and then move to blood stream all over the body, hence, you should take necessary precautions for avoiding continuous exposure to the chromium 6. It also results in kidney as well as liver damage, since it attempt to filter the toxins that are present in your body, which gets accumulated in your kidney and liver and results in kidney or liver failure.

There is concern whether in vivo corrosion of chromium-cobalt alloys releases ions containing trivalent [Cr(III)] or hexavalent [Cr(VI)] chromium. The question arises from indications that Cr(VI) is far more biologically active than Cr(III).

Here is MY  question: If it is possible for one form to change into the other when chemical conditions are right is there or should there be a concern about this "morphing" of one form of chromium to another?   Simiarly, I am concerned about this statement by  one of the law firms:  "Our research indicates that hexavalent chromium is the type of chromium being released by the ASR Acetabular system; it degrades in the body into trivalent chromium, or Chromium (III). Anywhere from 18-30% of a typical metal-on-metal implant is composed of chromium; we do not have current numbers on the amount of chromium included in the DePuy hip implant. (http://www.sullolaw.com/Article/chromiumpoisoning.html)


Well, this is exactly the issue addressed in this series of articles.  If this statement  is true, and I have no idea whether it is or isn't, the issue of hexavalent chromium is back on the table.  This research has lead me to the question:  Is the chromium in the depuy hip hexavalant which  is immediately oxidized to trivalant or are they claiming that the chromium is trivalent in its original state in the hip?  I have no clue.  This should be clarified by Depuy.  I can tell you that most of the articles on this topic address chromium oxidation interchangeably with Metal on Metal hips.

What does Wolf Say?

Carcinogenesis. 1989 Apr;10(4):655-9.

Molecular interaction of different chromium species with nucleotides and nucleic acids.

Source

Institut fur Arbeitsphysiologie, Dortmund, FRG.

Abstract

The interaction of chromium(III) and chromium(VI) with the phosphate groups of di- and triphosphate nucleotides were examined by 31P-NMR spectroscopy. Chemical shifts of the phosphate groups, indicating the formation of Cr-nucleotide complexes, could only be detected with Cr(III). When Cr(III) was generated from Cr(VI) by reduction with an excess of glutathione, nearly the same chemical shifts could be observed. This indicates that glutathione is not capable of trapping Cr(VI) by reduction with subsequent formation of stable Cr-GSH complexes, thus preventing the binding of chromium to important target molecules as DNA or nucleotides. Using radioactively-labelled chromium no 51Cr(VI) bound to any nucleic acid, whereas 51Cr(III) bound in increasing order to poly(A).poly(U), calf thymus DNA and poly(G).poly(C). Furthermore, the melting temperature of nucleic acids increased in the same order only in the presence of Cr(III). Possible genotoxic consequences in vivo of the presented data in vitro concerning the binding of Cr(III) to sensitive molecular targets are discussed in detail.

[ Well, I surely don;t understand all of the intracacises of this but what I gather from this is that Cr 3 binding to DNA is well documented.]

Tomorrow, I will look at Bacon and Marnett.

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