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More evidence nanoparticles damage DNA

Australian Broadcasting Corporation
November 6th, 2009

Researchers in the United Kingdom have found some nanoparticles - which can be found in common household items - can damage DNA without even penetrating the cells.

They found the nanoparticles can indirectly damage DNA inside cells by transmitting signals through a protective barrier of human tissue.

The stunning discovery adds to a growing body of research highlighting proven and potential health hazards from the rapidly expanding universe of engineered objects measured in billionths of a metre.

Nanoscale products already widely in use range from cosmetics to household cleaning products and sporting goods.

But the new findings, reported in the journal Nature Nanotechnology, could also point to new ways in which nanotherapies might zero in on disease-causing tumours, say researchers.

They could even shed light on how poorly understood pathogens penetrate into human organs.

In laboratory experiments, scientists led by Dr Charles Case of Southmead Hospital in Bristol, grew a multi-layer 'barrier' of human cells to mimic specialised protective tissues found in the body.

For example one such barrier separates blood from the brain.

Underneath this layer, three-to-four cells thick, they placed human fibroblast cells which play a key role in the formation of connective and scar tissue.

And on top they put nanoscale particles of cobalt-chromium, an alloy that has long been used in the making of hip-and-knee-replacement joints, and more recently in drug-delivery mechanisms used inside arteries.

'As if it weren't there'

Earlier studies had shown that direct exposure to large quantities of the alloy could severely damage DNA is some cells and the researchers wanted to find out how well the laboratory grown barrier would protect the fibroblast cells below.

"We never imagined that it wouldn't," said Dr Case.

"But to our great surprise, not only did we see damage on the other side of the barrier, we saw as much damage as if we had not had a barrier at all."

At first, the researchers speculated that the tiny particles, barely 30 billionth of a metre in diameter, had slipped through microscopic cracks in the cellular blockade.

But there was no sign of the alloy on the other side and when the experiment was repeated with far larger particles, the result was essentially the same.

"We could only conclude that the DNA damage occurred after indirect exposure depending on a process of signalling between cells rather than the passage of metal through the barrier," said Dr Gevdeep Bhabra, a surgeon at Southmead and co-author of the study.

Professor Thomas Faunce from the Australian National University in Canberra says the study is significant.

"Nano-toxicological research has focused on looking at what happens if we put nanoparticles inside these type of cells," said Professor Faunce.

"What [this latest research is] saying is once nanoparticles are in the body they have a capacity to cause toxocological effects at a distance."

Previously, Professor Faunce has expressed concern regarding the over-use of nanoparticles in products such as nano-silver bandages and undergarments.

He says in light of this recent report any future investigation into the use of nanoparticles and their associated levels of toxicity may need to be rethought.

His views were echoed by the researchers themselves and experts not involved in the study.

"What it tells me is that the precaution with which some scientists and regulators say we should proceed is the right way to go," said Professor Vyvyan Howard, a pathologist at the University of Ulster who founded the Journal of Nanotoxicology.

Prion diseases

But the newly uncovered mechanism holds promise too.

"The first exciting question is, can we deliver novel therapies across barriers without having to cross them?" said Professor Ashley Blom, an orthopaedic surgeon and researcher at the University of Bristol.

"There are also implications as to how nanoparticles that we all have in our bodies might act across membranes - small particles like prions and viruses may use some of these mechanisms.

"This opens up a whole new field of research."

Prion diseases occur when a mutated form of the prion protein runs amok, destroying brain cells.

Testing

Professor Howard says when considering the safety of nanoparticles, one must distinguish between medical and broader industrial applications.

New drugs are carefully tested, reducing the chances of widespread harm. And even if nanodelivery and imaging systems turn out not to be risk-free, that does not necessarily mean they should not be used.

"Depending on the kind of disease you have, you will accept some very nasty therapies," he said. For example a chemotherapy for cancer.

"But there is a world of difference between accepting a therapy under informed consent and involuntary exposure."

He pointed out most industrial uses are not regulated at all.