New nano-canary in the nanotoxicology coalmine: the body itself
With an eye on disembodied cells and virtual organs, researchers attempt to track biological changes as they occur
February 17, 2006
RICHLAND, Wash. –
There is growing consensus among scientists, regulators, politicians, industry and the public that we need to know more about the possible harmful or adverse effects of nanoparticles on human health.
Likewise, most agree that these incredibly small materials can behave quite differently from conventional materials. Nonetheless, neighborhood stores feature products that promise benefits from these near-atomic level materials, from paints and cosmetics to toothpaste and sunscreens. But, could we be putting human health at risk by exposing consumers to potentially toxic materials?
To investigate the damage potential of sub-micron sized particles, S.K. Sundaram and Thomas J. Weber, scientists at the Department of Energy’s Pacific Northwest National Laboratory in Richland, Wash., have harnessed living cells to monitor responses to a variety of toxins. They presented their findings Friday at the American Association for the Advancement of Science annual meeting.
“The process requires that live cells be grown on an infrared transparent substrate giving us an opportunity to closely examine the biological effects in living cells,” said Sundaram. Live cell Fourier transform infrared, FTIR, spectroscopy offers several attractive features for these investigations. These include the potential to detect biologically active nanoparticles without any prior knowledge of cell signaling pathways affected by them or need of a contrast agent to detect the biological response. Thus, live cell FTIR spectroscopy is expected to be a sentinel of exposure to help define nanoparticles that are biologically active, without bias of what that biological activity represents.
The PNNL scientists are also developing infrared transparent chemistries that are expected to improve FTIR measurements in live cell experiments. “We believe this is the first time FTIR spectroscopy has been used to examine the biological response of living cells to nanoparticles, and expect this technology will enable us to identify chemical changes associated with the biological response,” said Weber. FTIR spectroscopy measures a broad spectrum of chemical bonds and will provide information that is complementary to genomic and proteomic approaches.
FTIR spectra are captured in minutes in live cell studies, offering a tool for quick discovery of biomarkers of exposure that can determine whether nanoparticles are biologically active. This information can be used to prioritize nanoparticles for further study to ascertain the nature of the biological activity in terms of toxicity.
A broader approach to discovering what environmental nanomaterials can do once they enter the body – and how they enter and where they go – is being led by PNNL. This research is part of a $10 million, 5-year National Institutes of Health project designed to devise 3-D imaging and computational models that provide unsurpassed detail of respiratory systems in humans and other mammals.
Advancements in medical imaging, data analysis and computation have increased “the speed and accuracy of developing detailed models of the complete respiratory system,” reported Richard Corley, PNNL staff scientist and director of the multi-institutional study. “New imaging techniques also show promise for validating particle deposition models. Atlases of airway geometries and functional characteristics are also being constructed that will facilitate analyses of variability, reduce uncertainties in animal to human extrapolations and contribute to a more quantitative representation of environment-disease interactions.”
Pacific Northwest National Laboratory (www.pnl.gov) is a DOE Office of Science laboratory that solves complex problems in energy, national security, the environment and life sciences by advancing the understanding of physics, chemistry, biology and computation. PNNL employs 4,100 staff, has an annual budget of more than $700 million annual budget, and has been managed by Ohio-based Battelle since the lab's inception in 1965.
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The capability of measuring and modeling subcellular responses to toxins represents significant progress toward an important capability within PNNL’s Environmental Biomarkers Initiative. The EBI applies system science and pattern recognition to the discovery of biomolecular signatures. PNNL believes biomarkers provide the next generation of risk assessment tools, replacing whole-organism measures of response with directly measured sub-cellular responses from first exposure through terminal disease state.
Tags: Energy, Environment, Fundamental Science, National Security, Chemistry, Biology