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Single-Cell Analysis Reveals that Chronic Silver Nanoparticle Exposure Induces Cell Division Defects in Human Epithelial Cells

1
Department of Biological Sciences and Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA 24061, USA
2
Department of Civil and Environmental Engineering, Virginia Tech, Blacksburg, VA 24061, USA
3
Center for Cancer Research, National Institute of Health, Frederick, MD 21702, USA
*
Author to whom correspondence should be addressed.
Current affiliation: Lake Erie College of Osteopathic Medicine (LECOM) at Seton Hill, Greensburg, PA 15601, USA.
Current affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
§
Current: affiliation: Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO 80309, USA.
Int. J. Environ. Res. Public Health 2019, 16(11), 2061; https://doi.org/10.3390/ijerph16112061
Received: 20 December 2018 / Revised: 28 May 2019 / Accepted: 7 June 2019 / Published: 11 June 2019
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Abstract

Multiple organizations have urged a paradigm shift from traditional, whole animal, chemical safety testing to alternative methods. Although these forward-looking methods exist for risk assessment and predication, animal testing is still the preferred method and will remain so until more robust cellular and computational methods are established. To meet this need, we aimed to develop a new, cell division-focused approach based on the idea that defective cell division may be a better predictor of risk than traditional measurements. To develop such an approach, we investigated the toxicity of silver nanoparticles (AgNPs) on human epithelial cells. AgNPs are the type of nanoparticle most widely employed in consumer and medical products, yet toxicity reports are still confounding. Cells were exposed to a range of AgNP doses for both short- and-long term exposure times. The analysis of treated cell populations identified an effect on cell division and the emergence of abnormal nuclear morphologies, including micronuclei and binucleated cells. Overall, our results indicate that AgNPs impair cell division, not only further confirming toxicity to human cells, but also highlighting the propagation of adverse phenotypes within the cell population. Furthermore, this work illustrates that cell division-based analysis will be an important addition to future toxicology studies. View Full-Text
Keywords: silver nanoparticles; mitosis; nanotoxicology; micronucleus; tetraploidy silver nanoparticles; mitosis; nanotoxicology; micronucleus; tetraploidy
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Garcia, E.B.; Alms, C.; Hinman, A.W.; Kelly, C.; Smith, A.; Vance, M.; Loncarek, J.; Marr, L.C.; Cimini, D. Single-Cell Analysis Reveals that Chronic Silver Nanoparticle Exposure Induces Cell Division Defects in Human Epithelial Cells. Int. J. Environ. Res. Public Health 2019, 16, 2061.

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