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nanotimes News in Brief

11-09 :: September 2011

Toxicology // Nickel Nanoparticles may Contribute to Lung Cancer © Text: Brown University

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ew research by an interdisciplinary team of scientists at Brown University finds that na-

noparticles of nickel activate a cellular pathway that contributes to cancer in human lung cells.

“Nanotechnology has tremendous potential and promise for many applications,” said Agnes Kane, chair of the Department of Pathology and Laboratory Medicine in The Warren Alpert Medical School of Brown University. “But the lesson is that we have to learn to be able to design them more intelligently and, if we recognize the potential hazards, to take adequate precautions.”

Nickel nanoparticles had already been shown to be harmful, but not in terms of cancer. Kane and her team of pathologists, engineers and chemists found evidence that ions on the surface of the particles are released inside human epithelial lung cells to jump- start a pathway called HIF-1 alpha. Normally the pa- thway helps trigger genes that support a cell in times of low oxygen supply, a problem called hypoxia, but it is also known to encourage tumor cell growth.

“Nickel exploits this pathway, in that it tricks the cell into thinking there’s hypoxia but it’s really a nickel ion that activates this pathway,” said Kane, whose work is supported by a National Institues of Health Superfund Research Program Grant. “By activating this pathway it may give premalignant tumor cells a

head start.” A key finding is that while the smaller particles set off the HIF-1 alpha pathway, the larger metallic nickel particles proved much less problematic.

Another important result from the work is data showing a big difference in how nickel nanoparti- cles and nickel oxide nanoparticles react with cells, Pietruska said. The nickel oxide particles are so lethal that the cells exposed to them died quickly, leaving no opportunity for cancer to develop. Metallic nickel particles, on the other hand, were less likely to kill the cells. That could allow the hypoxia pathway to lead to the cell becoming cancerous.

“What is concerning is the metallic nickel nanopar- ticles caused sustained activation but they were less cytotoxic,” postdoctoral research associate and first author Jodie Pietruska said. “Obviously a dead cell can’t be transformed.”

Jodie R. Pietruska, Xinyuan Liu, Ashley Smith, Kevin McNeil, Paula Weston, Anatoly Zhitkovich, Robert Hurt, and Agnes B. Kane: Bioavailability, intracellular mobi- lization of nickel, and HIF-1a activation in human lung epithelial cells exposed to metallic nickel and nickel oxide nanoparticles, In: Toxicological Sciences, Advance Access, August 9, 2011, DOI:10.1093/toxsci/kfr206: http://dx.doi.org/10.1093/toxsci/kfr206