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Silver nanoparticles: correlating nanoparticle size and cellular uptake with genotoxicity.
Kimberly S Butler1, David J Peeler1, Brendan J Casey1
1U.S. Food and Drug Administration, Office of Medical Products and Tobacco, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Biology, Chemistry, and Materials Science, 10933 New Hampshire Avenue, Silver Spring, MD 20993, USA.
Mutagenesis
|May 13, 2015
Summary
Silver nanoparticles (AgNPs) did not show mutagenicity in bacteria. In mammalian cells, smaller AgNPs induced more genotoxicity, likely due to silver ions, not nanoparticle uptake.
Area of Science:
- Nanotechnology
- Toxicology
- Genetics
Background:
- Silver nanoparticles (AgNPs) are increasingly used, necessitating an understanding of their genotoxic potential.
- Cellular uptake mechanisms are critical for determining nanoparticle toxicity.
- Investigating AgNP genotoxicity requires assessing mutagenicity, clastogenicity, and DNA damage.
Purpose of the Study:
- To investigate the genotoxicity of silver nanoparticles (AgNPs) across various sizes.
- To determine the influence of cellular uptake on AgNP-induced genotoxicity.
- To elucidate the mechanisms of AgNP genotoxicity, including the role of silver ions.
Main Methods:
- Bacterial reverse mutation assays (Ames test) were performed on Salmonella typhimurium and E. coli strains.
- Mammalian cell lines (Jurkat and THP-1) were used for clastogenicity (micronucleus assay) and DNA strand break assessment (Comet assay).
- Transmission electron microscopy (TEM) was employed to visualize AgNP cellular uptake.
Main Results:
- AgNPs and silver nitrate (AgNO3) were not mutagenic in bacteria.
- Bacterial cells did not show uptake of AgNPs (10nm or larger).
- Genotoxicity in mammalian cells (micronucleus and Comet assays) was inversely correlated with AgNP size, with smaller nanoparticles being more potent.
- AgNPs were observed within intracellular vesicles in mammalian cells, not penetrating the nucleus.
Conclusions:
- Silver ions, rather than AgNPs themselves, appear to be the primary drivers of genotoxicity.
- The lack of bacterial genotoxicity is likely due to silver ions, not solely the absence of AgNP uptake.
- Smaller AgNPs exhibit greater genotoxic effects in mammalian cells, highlighting the importance of size-dependent nanoparticle properties.
