Tuesday, May 15, 2012

Oxidative Stress process associated with Metal on metal hips (series 4 of x)

This is a series of articles on Oxidative Stress which results in DNA changes and potentially cancer

Oxidative Stress process associated with Metal on metal hips (series 3 of x)
Advances in metal-induced oxidative stress and human disease. (2 of x in a series)
Advances in carcinogenic metal toxicity and potential molecular markers. (1 of x in a series)

"Different pathways are used by metal ions to enter into the cells. Cr (chromium) 6 can cross the cytoplasmic membrane through the non-specific phosphate/sulfate anionic transporters.  Within the cell, Cr6 undergoes rapid metabolic reduction to form Cr 5, then Cr4 and finally  Cr 3.

At each step, of Cr reduction from Cr6, reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated.  Whether or not Cr 3 is able to cross the cell membrane on its own without a carrier remains controversial.  Co (cobalt)2 can cross the cell membrane using the non-specific ion transporter and it is oxidized in the cytosol to Co 3.  Co-oxidation leads to the generation of ROS and TNS.  Co 2 and CR 6-3 can also bind some metal-binding proteins such as transferrin or ferritin.  In the endosome, Co 2 and Cr 6-3 are unbound from their protein carrier via the DMT1 transporter.  They are released in the cytosol where they can be reduced or oxidized and result in the generation of ROS/RNS. ROS and RNS are known to be involved in the oxidation, leading to their degradation,lipid perodixation and DNA damage. Cr 3 can also cross the nuclear membrane and particpate in alteration of DNA.

Metal particles  released from the articulating surface of the MoM prosthesis can be phagocytosed by the cells.  Inside the phago-lysosome, particles become corroded and release metal ions in the cystol."

Reference source: page 743

Acta Orthop. 2008 Dec;79(6):734-47.

Metal-on-metal hip resurfacing arthroplasty: a review of periprosthetic biological reactions.


Nuffield Department of Orthopaedic Surgery, Institute of Musculoskeletal Science, Botnar Research Centre, University of Oxford, Oxford, UK. guillaume.mabilleau@ndos.ox.ac.uk
[All of this matters in terms of trying to get to the bottom of whether these metals can cause cancer.  The more research done in this area, the better.  I hope this series helps you see the possible connections between metals being able to cross the cell barrier resulting in changes in DNA which can potentially result in cancer.
I have a recurrent cancer that was arrested and seemed to come back mysteriously after this revision surgery.  I am investigating the links and will be seeing the top Oncologists in the world over the next two weeks before I start any kind of treatment and will share any information I have.)

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