Nanoparticles of nickel activate a cellular pathway that may contribute to human lung cancer, reveals research.
"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."
Kane is the senior author of the study published in advance online this month in the journal Toxicological Sciences.
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 jumpstart a pathway called HIF-1 alpha. Normally the pathway 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."
Size matters
The research team, led by postdoctoral research associate and first author Jodie Pietruska, exposed human lung cells to nanoscale particles of metallic nickel and nickel oxide, and larger microscale particles of metallic nickel. 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.
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