Sunday, May 13, 2012

Oxidative Stress process associated with Metal on metal hips (series 3 of x)

This is  the 3rd in a series on Oxidative Stress and its relationship to cancer.  This is  follow on from the prior two articles:
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)

I was reading these two prior articles on the oxidative stress process which results in carcinogens from Chromium and cobalt  and recalled reading this exact same process from this article done by the guys at Oxford University:

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

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

Source

Nuffield Department of Orthopaedic Surgery, Institute of Musculoskeletal Science, Botnar Research Centre, University of Oxford, Oxford, UK. guillaume.mabilleau@ndos.ox.ac.uk

Now this article reviewed the periprosthetic biological reactions of the metal on metal arthroplasty.

Here is the section on  page 742 called :  metal induced intracellular effects.  Sounds very much like the prior two articles printed in 2011 but from a different perspective.

"Reactions with metal ions can lead to generation of free radicals:  reactive oxygen species (ROS) and ractive nitrogen species (RNS) which can in turn, cause cellular dysfunction.  In side the cells, Cr6 is oxidized to Cr3." [Now remember, Cr 6 is the most toxic of the Chromiums however, it is in fact the metal that appears to first be introduced via the metal on metal hips.]......."Permanent modification of gentic material resulting from this oxidative damage represents the first step in mutagensis, carcinogensis and ageing... direct binding of Cr3 to DNA is well documented.  In cells, 2 main processes exist to correct DNA aberrations and to restore the integrity of the genome:  excision repair (BER) and neculeotide excision repair (NER).  Under stimulation by Co2 and Cr6, both of these mechanisms are inhibited."

[It looks like the same process of the oxidative stress is present with the hip revisions.  it also sounds as though this oncogenic stimulation is present.  Unfortunately, this chemistry is way beyond me.  I have consults arranged with the top cancer centers to try and get some better insight into this material. 

My concern is the following:

(1) Should I be placed on Chemo like treatment when I have been exposed to the amount of metals that I have?
(2) Is it possible that my tumors will shrink as the metal levels receded from the revision?
(3) Is it possible that I had some orphan dormant cells that were activated during the revision with the amount of stress that my body was under with the exceedingly high levels of metals that get released during revisions?

How does all of the effect my treatment for Stage 4 renal cell at this point?

Tomorrow I will discuss the pathways used by metal ions to enter into the cells which is a really important point to understand if you have the questions that I do. 
 

2 comments:

  1. Connie, the questions you ask re your own treatment are essential, and my guess is that no one really knows the answers. I'm worried about how you and your treatment team make good decisions going forward. Keep us posted. You are always in our thoughts and prayers. Pam

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  2. Hi Pam,

    You may be right. No one may know. What concerns me is starting on a chemo regimen when I still have very high metal levels, albeit they are down from the pre revision rates.

    I would like to understand what it means to mix high levels of metals with high levels of chemicals and whether this is really a good idea.

    I have 3 appointments scheduled with the top cancer centers for second opinions and this will be at the top of my agenda.

    I still have no results from the cyto gentetic tests but do have preliminary results on the metal measurment tests in the organs which I will report on as soon as I have the write ups.

    I think this is a puzzle and every piece adds information. Hopefully, once I am finished with the consults, the puzzle will be more complete OR NOT.

    Thanks for checking in.

    Connie

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