Tuesday, July 26, 2011

Review of the Cell biology surrounding metal on metal hips (8 of x in a series)

The material for this series of posts  is sourced through the the following journal article:

Acta Orthop. 2008 Dec;79(6):734-47.
Metal-on-metal hip resurfacing arthroplasty: a review of periprosthetic biological reactions.
Mabilleau G, Kwon YM, Pandit H, Murray DW, Sabokbar A.

Metal-induced intracellular effects- metal of concern is Cobalt and Chromium 3 found in the Depuy hip.

1. Reactions with metal ions can lead to generation of free radicals which can, in turn, cause cellular dysfunction.

2.  Inside the cells, Chromium( Cr)6 is oxidized to Cr 3 in a series of steps that generate free radicals.
(Chromium 6 -the toxic form of Chromium-  Chromium 3, -purportedly the non toxic form of Chromium found in the Depuy hip.-

3.  Cobalt (Co) ions can also lead to the generation of free radicals.

4.  Free radicals can react with DNA and induce damage to the building blocks of DNA.

5.  Permanent modification of genetic material resulting from this "oxidative damage" represents the first step in mutagenesis*, carcinogenesis** and ageing.

*mutagenesis-process by which the genetic information of an organism is changed.
**carcinogenesis-is literally the creation of cancer.

6.  Although no evidence has been found for direct binding of Co2 to DNA, direct binding of Cr3 to DNA is well documented (Wolf et al, 1989)

7.  Two main processes exist to correct DNA aberrations and to restore the integrity of the genome.

8. Both of these repair mechanisms are inhibited.

9.  Landon investigated changes in metal ion levels and chromosome aberrations in patients within 2 years  of receiving Metal on Metal hips.  The authors noted an increase in translocations* and aneuploidy** in peripheral blood lymphocytes at 6, 12 and 24 months after surgery.

*Translocations-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.

**aneuploidy- is an abnormal number of chromosomes, and is a type of chromosome abnormality. An extra or missing chromosome is a common cause of genetic disorders (birth defects). Some cancer cells also have abnormal numbers of chromosomes.

10.  The authors however, did not find any statistically significant correlations between chromosomal translocation indices and Co or Cr concentrations in whole blood.

[  connie:  so what about the abnormal number of chromosomes?]

conclusions tomorrow....

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