Monday, October 8, 2012

More on Nanoparticles causing DNA damage from MOM hips through oxidatve stress (6 of x in a 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

Discussing the 3rd of 4 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 intial post above.

  Journal article we are discussing in this post:  Signalling of DNA damage and cytkines 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.)

1.  It has been shown that nanoparticles can cause oxidative injury through the generation of reactive oxygen species (ROS) and it has been recommended that the postential toxic effects of nanomaterials should be carefully evaluated before they are introduced into consumer products.

2.  Cell barriers offer important protection against  particle exposure and exist in several forms within the body.

3.  These authors have shown previously that cobalt and chromium nanoparticles on one side of a multi layered cell barrier can cause DNA damage and aberrations in the chromosomes of cells on the other side without passing through the barrier.

4.  It was therefore of interest to test whether these indirect effects of nanoparticles might vary for different types of barrier.

5. Nanoparticle exposure  caused a short -term increase in free radical cells but Vitamin C was effective in preventing DNA damaging signalling from the nanoparitcle-exposed barriers.( Vit C is  known combatent of oxidative stress.)

[ from connie...this is quite amazing as I have independently come to the conclusion that high dose IV vitamin C might serve as a protector  or neutralizer of the free radical electrons that are produced by these metals!  Just from my own experience, if these aren't controlled, dormant cancer cells may very well become active and metastasize...this is a very practical article albeit, hard to understand from a lay perspective]

6.  Their data supported there being a role for mitochondrial derived free radicals in the transbarrier DNA-damaging signals.

7.  Transbarrier signalling resulting in DNA damage might be significant  in human pregnancy.

8.  The experiments implied this gap mediated signalling process varies with gestational statge.

9.  The fetus is most vulnerable to DNA and oxidative damage early in pregnancy.  They then tested this to determine whether this signalling has the potential of damaging embryos.

10.  No pathological changes were noted but there was a 2.x fold increase in DNA damage in neonatal blood after exposure and a much smaller increase in DNA damage to the neonatal liver and no increase in DNA damage was seen in the maternal brain.  The levels of Cr and Co had not increased in the neonates. 

11.  Cr and Co are the main components of the CoCr ally and are known to accumlate in CoCr particle-exposed tissues but no difference was seen in the morphology of the organs after sectioning of the paraffin embedded tissue.

12. Signalling was then tested in expants of human placenta in the first trimester when the barriers have the bi- layered and in later phases of pregnancy when the cell bariers are  monolayered .

13.   They then altered the oxygen from 1% to 21% as this stimulus had been found to cause the cell barriers to send DNA damaging signals to fibroblasts.

14.  When the media  surrounding the first trimester  explants was then transferred to fibroblasts,  an  increase in DNA damage was observed in the fibroblasts but not observed for the third trimester explants.

15.  They then looked at signalling through corneal cells determine whether the signalling was cell specific.  Same results.  DNA damage was observed in the fibroblasts below the nanoparticle exposed bilyaerd barriers but not below the the monlayered barriers.  This DNA damage was blocked by Vitamine C.

17.  There were some differences between the nanoparticles exposed to the BeWo and corneal barriers. The corneal bilayers secreted Cytokines (inflamatory enzymes) generated by oxidative stress which was blocked/prevented by Vit C. 

18.  The cytokines were secreted from cell barriers which is a novel finding....Could these signals be age or disease related?

The conclusions:
  • nanaoparticles can cause direct damage in vitro across cell barriers and can cause cytokine enzymes release across corneal barriers.
  • direct toxicity is possible in mice and from human placental tissue.
  • signals for DNA damage can cross the cell barriers through a pathway that involves gap junctions.
  • the types of signalling were noted only when the barriers were bilayered and multilayered.
  • If this is a general feature for all barriers, it offers a principle to apply to nano toxicity that may not only limit the adverse effects of nanoparticle exposure but may also offer some novel therapeutic possiblities.
Please remember, this is my interpretation of the study.  I am not a biochemist so getting through this material was difficult and I may have omitted some important items.   If you wish to review this study , you can see the citation for it in the URLS above.

The last study in this series was published in 2012.  I will review that study in a few days

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