Monday, October 15, 2012

More on Nanoparticles causing DNA damage from MOM hips through oxidatve stress (7 of 7 in a series/final post in this series)

Prior posts in the sequence
1 of x
More on Nanoparticles causing DNA damage from MOM hips with oxidative stress ( 1 of x in a series)
2 of x
3 of x
4 of x
5 of x
6 of x

Discussing the 4th of 4 studies which I think are  seminal works on the issues related to causing free radicals in the cell environment from MoM: Nanonparticles can cause DNA damage across a cellular barrier. You can get a background on this subject matter in terms of definitions by starting with the initial post above.

Journal article we are discussing in this post: Signalling of DNA damage and cytokines across cell barriers exposed to nanoparticle3s depends upon barrier thickness

The first study in this series established that the group of scientists demonstrated there is both cytotoxic and genotoxic effects of nanoparticles of cobalt chrom alloy in a tissue culture using human fibroblasts. /The research on that article was done in 2007.

The second study was published in 2009 and goes a step further to show that the nanoparticles from metals can damage human fibroblast cells across the cell barrier without having to cross the barrier. these would be categorized as indirect effects when evaluating the safety of nanoparticles in the body.

The third study shows that indirect DNA damage from the metals depends on the thickness of the cell barrier and it is generated by certain signals from the free radicals. Signalling includes the release of cytokines. (Study done in 2011.)

The forth and final study uses spectromicroscopy of the tissues surrounding the failed Co Cr metal on metal hip which demonstrate the mitochondrial damage that occurs at the cellular level from the metal oxidation. (Study done this year in 2012)

1.  The oxidation state of metals can provide vital clues to the inflammatory response (such as the generation of oxidising species) as well as providing valuable clinical information on the release of Co or Cr.

2.  Few techniques are capable of probing the exact chemical state of these particles with  sufficient spacial resolution.

3.  It is hypothesised that poor human biocompatibility with nanoscale wear debris is responsible for the early failur of MoM hips.

4.  It is not known how wear debris interacts with the tissue nor which metallic species (physical or chemical properties) is responsible for the failure of  these devices

 5.  Findings:
  • Most macrophages*  appeared to be packed with electron dense particles.
  • Their mitochondria* appear swollen
  • These findings are consistent with the effects of oxidant stress. 
*Macrophages are cells that  phagocytose, or engulf and then digest, cellular debris and pathogens

*Mitochondria are sometimes described as "cellular power plants" because they generate most of the cell's supply of adenosine triphosphate (ATP), used as a source of chemical energy.[2] In addition to supplying cellular energy, mitochondria are involved in other tasks such as signaling, cellular differentiation, cell death, as well as the control of the cell cycle and cell growth

6.  The observation that CoCr particles cause mitochondrial toxicity in the absence of cytotoxicity has been reported in fibroblast cells...[ note from connie:  interesting because it seems to suggest that the cell doesn't damage but the signalling in the cell is damaged.

7.  In agreement with previous studies, their study showed that wear debris was present in two morphologies:
  • dense nanoparticles and  diffuse material.
  • the debris was composed mostly of Cr3.
  • the particles were internalized inside the cell membrane compartments inside the macrophage cells.
8.  Their conclusion was that while there is a lot of concern on the potential generation of the genotoxic Cr 6, their data suggest a significant localized release of genotoxic Co2


This study matters because not only are we faced with the oxidation of Cr 6 to Cr 3 but now we are faced with the oxidation of Co 2 which is genotoxic.  This study has actually produced photography of these reactions.

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