Tuesday, October 11, 2011

Review of the Implications of MOM hips to cancer addressing the creation of abnormal chromosomes (genotoxic effects-2 posts back-), Immune Mediated responses (last post) and oxidation of Cr 3 to 6 and visa versa-below-. (3 of 3)

Oxidative Damage / exerpts from  Acta Orthopaedica 2008 79 (6) 734-747 University of Oxford
//Metal-induced intracellular effects

1.  Reactions with metal ions can lead to generation of free radicals:  reactive oxygen species (ROS) and reactive nitrogen species (RNS) which in , cause cellular dysfunction. 

2.  Inside the cells, Cr 6 is oxidized to Cr 3 in a series of steps that generate free radicals.

3.  Free radicals catalyze the oxidation of protein and phospholipids.

4.  That process leads to the formation of malondialdeyde which can react with DNA bases to form DNA protein cross links

5.  Permanet modification of genetic material resulting from this oxidative damage represents the first step in mutagenesis and carcinogenesis.

6.  Direct binding of Cr 3 to DNA is well documented.

7.  In cells , two main processes exist to correct DAN aberrations to restore the integrity of the genome.

8.  Under stimulation by Cobalt 2 and Chromium 6, both of these mechanisms are inhibited.

9.  Landon (2004) investigated changes in metal ion levels and chromosome aberrations in patients within two years of receiving metal on metal atheroplasties.

10  The authors noted an increase in chromosome translocations and aneuploidy in peripheral blood lymphocytes at 6, 12, 24 months after surgery.

  • Aneuploidy is an abnormal number of chromosomes, and is a type of chromosome abnormality. Some cancer cells have abnormal numbers of chromosomes.[1] Aneuploidy occurs during cell division when the chromosomes do not separate properly between the two cells...The question is what is the relationship between the metal on metal hip and long term systemic effects with things like cancer?

  • In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer.

11.  The authors noted the changes were progressive.

12.  The authors didn't find any statistically significant correlations over those short time frames between chromosomal translocations and Co and Cr concentrations in the whole blood.

following are some summary steps of this oxidation process.  A bit technical but helpful:

  • Different pathways are  used by metal ions to enter the cells
  • Chromium 6 can cross the cell membrane
  • Chromium 6 undergoes rapid metabolic reduction to form Chromium 5, chromium 4 and then chromium 3.
  • At each step of the Cr  6 reduction, ROS and RNS are generated (see above for definition of these terms)
  • Cr 3 can cross the cell membrane and participate in alteration of DNA.
So my question remains, did we start with Chromium 6 which was oxidized to Chromium 3 in our body?  Yes or No?  If yes, and the oxidation process is a known cause of DNA damage and is the first step in carcinogenesis and mutagenesis, is this not a problem?

I think I have to call these authors from Oxford to get an answer to this question.  The general orthopedic surgeons do not know the answer to this question.  I think it is important to know whether Chromium 3 (less carcinogenic material than Chromium 6) is oxidized from Chromium 6 (highly toxic) or not.

These 3  posts pose all of the questions that are bothersome to me re the long term systemic effects of Chromium, the immune system and carcinogenic effects.

Maybe no one knows the answer?

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