Mutagenicity of silver nanoparticles evaluated using whole-genome sequencing in mouse lymphoma cells

Abstract

The increasing medical and food applications of silver nanoparticles (AgNPs) raise concerns about their safety, including the potential health consequences of human exposure. Previous studies found that AgNPs were negative in the Ames test due to both their microbicidal activity and the inability of nanoparticles to penetrate bacterial cell walls. Thus, the mutagenicity of AgNPs is still not completely clear, though they do induce chromosome damage, as suggested by many previous genotoxicity studies. In this study, whole-genome sequencing (WGS) was used to analyze the mutagenicity of AgNPs in mouse lymphoma cells expanded from single-cell clones. The cells were treated with AgNPs, 4-nitroquinolone-1-oxide (4-NQO) as the positive control, and vehicle controls. Both AgNPs and 4-NQO significantly increased mutation frequencies over their concurrent controls by 1.12-fold and 4.89-fold with mutation rates at 4-fold and 130-fold, respectively. AgNP-induced mutations mainly occurred at G:C sites with G:C > T:A transversions, G:C > A:T transitions, and deletions as the most commonly observed mutations. AgNPs also induced higher fold changes in tandem mutations. The results suggest that the WGS mutation assay conducted here can detect the low-level mutagenicity of AgNPs, providing substantial support for the use of the WGS method as a possible alternative assay with respect to the mutagenic assessment of nanomaterials.

Keywords:

• Silver nanoparticles
• mutagenicity
• whole-genome sequencing
• mutation spectrum

Acknowledgments

This project was supported by appointments (BP, PK, AA, and HD) to the Postgraduate Research Program at the NCTR administered through the Oak Ridge Institute for Science and Education through an interagency collaboration between the U.S. Department of Energy and the U.S. Food and Drug Administration.

Disclosure statement

No potential conflict of interest was reported by the author(s).