Nanometer and Micrometer Particles
Cause DNA Damage Across Cell Barriers
As nanotechnology continues to come under fire for lack
of known effects, a study now finds that tiny metal particles
have been shown to cause damage to DNA across a cellular barrier
- without having to cross it.
The nanometer and micrometer scale particles resulted in an increase
of damage to DNA across the barrier via a never-before-seen cell
Reporting in Nature Nanotechnology, the researchers say the mechanism
could be both a risk and an opportunity.
They say the preliminary result is relevant as more medical therapies
rely on small-scale particles.
For instance, nanoparticle-based approaches are being considered
for use to improve MRI images or direct the delivery of cancer
However, they concede their model system is far simpler than
the human body, where the effects will be harder to unpick.
As yet, the researchers are not even certain of the mechanism
by which the signalling molecules cause damage to DNA.
The team studied the effects of particles made from cobalt and
chromium, either 30 billionths of a metre or four millionths of
a metre across.
These metals are used in implants such as artificial hips or
They grew a thin, artificial membrane from human cells and placed
the particles on the membrane. Beneath it, they placed fibroblast
cells, which in the body help to form connective tissue.
Although the team showed that the particles had not crossed the
membrane, the fibroblast cells beneath were shown to have about
10 times as many damage sites in their DNA than the case in which
no particles were used.
Gevdeep Bhabra, lead author on the research from the Bristol
Implant Research Centre, explained that cells in close contact
are known to exhibit cell-to-cell communication through structures
known as gap junctions and hemichannels.
The signalling may well affect much more than just DNA changes
"We used a variety of chemicals to block this cell-to-cell
signalling and found that in the presence of these blockers, the
damage we were seeing was completely prevented," he said.
The team stressed that the concentrations of the particles were
thousands of times higher than would be found in the human body,
for instance from wear and tear on implants.
However, its discovery suggests that there is much work to be
done to establish if the mechanism that appears to be responsible
for the DNA damage is limited to those materials, or can occur
in the presence of other materials of a similar size.
That issue is of particular importance as more therapeutic and
imaging approaches begin to make use of nano-scale materials.
Ashley Blom, head of orthopaedic surgery at the University of
Bristol, explained that although the signalling could pose a future
risk, once understood it could be put to good therapeutic use.
"If the barriers in the human body do work in this way,
the first exciting thing is: can we deliver novel therapies across
barriers without having to cross them?
"For example, if you have a condition that affects the brain,
maybe we could treat you with something that doesn't cross the
blood-brain barrier, that does not come in contact with the brain."
Reference Source 108
November 7, 2009