Dataset Information

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.

SUBMITTER: Garcia EB

PROVIDER: S-EPMC6603987 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Garcia Ellen B EB Alms Cynthia C Hinman Albert W AW Kelly Conor C Smith Adam A Vance Marina M Loncarek Jadranka J Marr Linsey C LC Cimini Daniela D

International journal of environmental research and public health 20190611 11

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 ...[more]

PMID: 31212667

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Project description:In spite of many reports on the toxicity of silver nanoparticles (AgNPs), the mechanisms underlying the toxicity are far from clear. The present study conducted transcriptome and microRNAome sequencing for Euplotes vannus to understand the molecular mechanisms by which this protist copes with AgNPs exposure. By transcriptome profiling, 1884 and 5834 differentially expressed genes (DEGs) were identified after one hour and 12 hours exposure to 15 mg/L AgNPs, respectively. From microRNAsome profiling, totally 16 differentially expressed microRNAs were identified under AgNPs stress.In spite of many reports on the toxicity of silver nanoparticles (AgNPs), the mechanisms underlying the toxicity are far from clear. The present study conducted transcriptome and microRNAome sequencing for Euplotes vannus to understand the molecular mechanisms by which this protist copes with AgNPs exposure. By transcriptome profiling, 1884 and 5834 differentially expressed genes (DEGs) were identified after one hour and 12 hours exposure to 15 mg/L AgNPs, respectively. The DEGs were significantly enriched in macropinocytosis and phagocytic vesicles suggesting that the uptake of AgNPs may be mediated by endocytic pathways, while the differential expression of ABC transporters and copper-transporting ATPase implicates active efflux transport of Ag. Several DNA repair pathways were also significantly enriched with differentially expressed cell cycle control genes implying that exposure to AgNPs might have caused DNA damage and G2/M cell cycle arrest. The damage might have resulted from increased ROS production, as evidenced by elevated expression of several antioxidants genes to combat oxidative stress. From microRNAsome profiling, totally 16 differentially expressed microRNAs were identified under AgNPs stress. Integrated analysis of the microRNA and mRNA expression profiles found that the differentially expressed microRNAs target a series of genes involved in many important biological processes, suggesting that E. vannus exposure elicited a broad post-transcriptional regulatory mechanism through microRNAs–mRNAs–biological functions network to cope with the toxicity of AgNPs.

Dataset Information

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

Publications

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

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