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

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.

Proteomic Response of Aedes aegypti Larvae to Silver/Silver Chloride Nanoparticles Synthesized Using Bacillus thuringiensis subsp. israelensis Metabolites

“…Chromosome missegregation during mitosis has been reported to arrest the cell cycle as an effect following exposure to AgNPs [ 68 ]. Condensin is a hetero-pentameric protein complex that is essential for chromosome organization, such as mitotic chromosome assembly and segregation, and DNA recombination and repair processes [ 69 , 70 ].…”

Transcriptome Profile Alterations with Carbon Nanotubes, Quantum Dots, and Silver Nanoparticles: A Review

“…In humans, AgNP exposure has been linked to disrupting the function of mitochondria, sperm cells, and cytokine expression [ 47 ]. There are also reports of cell defects and induced inflammation [ 60 , 61 ]. Studies on AgNP toxicity are widespread in focus; we were specifically interested in the effect of AgNPs on gene function and transcriptome alterations across species.…”