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But could these microscopic spheres represent a
potential environmental hazard?
A new study published in December 2005 in
Biophysical Journal raises a red flag regarding the safety of
buckyballs when dissolved in water. It reports the results of a
detailed computer simulation that finds buckyballs bind to the spirals
in DNA molecules in an aqueous environment, causing the DNA to deform,
potentially interfering with its biological functions and possibly
causing long-term negative side effects in people and other living
organisms.
The research, conducted at Vanderbilt by chemical
engineers Peter T. Cummings and Alberto Striolo (now a faculty member
at the University of Oklahoma), along with Oak Ridge National
Laboratory scientist Xiongce Zhao, employed molecular dynamics
simulations to investigate the question of whether buckyballs would
bind to DNA and, if so, might inflict any lasting damage. "Safe is a
difficult word to define, since few substances that can be ingested
into the human body are completely safe," points out Cummings, who is
the John R. Hall Professor of Chemical Engineering and director of the
Nanomaterials Theory Institute at Oak Ridge National Laboratory.
"Even common table salt, if eaten in sufficient
quantity, is lethal. What we are doing is looking at the mechanisms of
interaction between buckyballs and DNA; we don't know yet what
actually happens in the body," he says.
Surprising findings
Despite the caveat, Cummings suggests that his
research reveals a potentially serious problem: "Buckyballs have a
potentially adverse effect on the structure, stability and biological
functions of DNA molecules."
The findings came as something of a surprise,
despite earlier studies that have shown buckyballs to be toxic to
cells unless coated and to be able to find their way into the brains
of fish. Before these cautionary discoveries, researchers thought that
the combination of buckyballs' dislike of water and their affinity for
each other would cause them to clump together and sink to the bottom
of a pool, lake, stream or other aqueous environment. As a result,
researchers thought they should not cause a significant environmental
problem.
Cummings' team found that, depending on the form
the DNA takes, the 60-carbon-atom (C60) buckyball molecule can lodge
in the end of a DNA molecule and break apart important hydrogen bonds
within the double helix. They can also stick to the minor grooves on
the outside of DNA, causing the DNA molecule to bend significantly to
one side. Damage to the DNA molecule is even more pronounced when the
molecule is split into two helices, as it does when cells are dividing
or when the genes are being accessed to produce proteins needed by the
cell.
"The binding energy between DNA and buckyballs is
quite strong," Cummings says. "We found that the energies were
comparable to the binding energies of a drug to receptors in cells."
It turns out that buckyballs have a stronger
affinity for DNA than they do for themselves. "This research shows
that if buckyballs can get into the nucleus, they can bind to DNA,"
Cummings says. "If the DNA is damaged, it can be inhibited from
self-repairing."
Computer simulations
The computer simulations showed that buckyballs
make first contact with the DNA molecule after one to two nanoseconds.
Once the C60 molecules bind with the DNA, they remained stable for the
duration of the simulation.
Researchers tested the most common forms of DNA,
the "A" and "B" forms. The "B" form is the most common form. In a
stronger saline solution, or when alcohol is added, the DNA structure
can change to the "A" form. A third, rarer form, "Z," occurs in high
concentrations of alcohol or salt and was not tested.
The researchers found that buckyballs docked on the
minor groove of "A" DNA, bending the molecule and deforming the
stacking angles of the base pairs in contact with it. The simulations
also showed that buckyballs can penetrate the free end of "A" form DNA
and permanently break the hydrogen bonds between the end base pair of
nucleotides.
As expected, the buckyballs bound most strongly to
single helix DNA, causing the most deformation and damage. While
buckyballs did bind to "B" form double-strand DNA, the binding did not
affect the overall shape of the DNA molecule. More research needed
What the researchers don't know is whether these
worrisome binding events will take place in the body. "Earlier studies
have shown both that buckyballs can migrate into bodily tissues and
can penetrate cell membranes," Cummings says. "We don't know whether
they can penetrate a cell nucleus and reach the DNA stored there. What
this study shows is that if the buckyballs can get into the nucleus
they could cause real problems. What are needed now are experimental
and theoretical studies to demonstrate whether they can actually get
there. Because the toxicity of nanomaterials like buckyballs is not
well known at this point, they are regarded in the laboratory as
potentially very hazardous, and treated accordingly." |
