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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 signal process.

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 drugs.

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.

Communication skills

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 knees.

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

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