Nanoparticles’ indirect threat to DNA

Tiny metal nanoparticles can damage DNA, essentially by triggering toxic gossip.

Researchers from throughout the United Kingdom took part in a series of tests in which they separated toxic metal nanoparticles from potentially vulnerable test cells — what I’ll refer to as cellular guinea pigs. In some cases the barrier was a piece of plastic, other times a four-cell-thick, intact wall of tissue.

Although the plastic wall protected the guinea pigs, “We found there was as much damage on the [far] side of the cellular barrier as there was if a barrier hadn’t been there in the first place,” observes C. Patrick Case, a researcher and pathologist at Southmead Hospital in Bristol, England. The finding, he admits, was “a huge surprise.” Particularly since the billionth-of-a-meter-scale particles appear to have wreaked their havoc indirectly.

When tests indicated the nanoparticles were not breaching the cellular wall, Case’s team began probing for evidence of some type of cellular signaling that might relay a damaging message to the DNA of cells on the opposite side. 

And indeed, the researchers report today in Nature Nanotechnology, the metal nanoparticles triggered the generation of ATP, a known signaling molecule, within cells of the barrier wall. ATP — and perhaps a chorus of related, but as yet unrecognized signaling molecules — whispered their chemical vitriol to neighboring cells.

The final layer of that wall then spit out its toxic message, which triggered within the hapless guinea-pig cells a splitting of one or more of the outer rails in their DNA’s ladderlike structure.

The damage was bad — but also improbable. Keep in mind, Case warns, “We were not trying to model what happens in humans.”

For instance, the UK scientists used unreal concentrations of nanoparticles. They also acknowledge that animals and people have evolved repair mechanisms to splice damaged DNA back together or to cull affected cells. However, those repair systems do sometimes become overwhelmed, repairing the DNA shoddily or allowing somewhat damaged DNA to persist. In these circumstances, disease — notably cancer — may develop.

Working in an orthopedics department, the team’s leaders also didn’t design their tests to use garden variety nanoparticles: carbon nanotubes or beads of nanosilver. Instead, they took tiny pieces of the cobalt-chromium alloy used in joint-replacement parts. Over time, shavings can wear off and end up surrounding joints, and perhaps even become excreted. The researchers also didn’t recruit ordinary, healthy cells as their guinea pigs but an experimental line — known as BeWo — which has been derived from placental cells.

In the future, Case says, his team plans to work with more conventional nanomaterials and in experimental systems that may better predict whether and how such teensy bits might prove toxic to the body.