Silver nanoparticles elevate mutagenesis of eukaryotic genomes

Area of Science:

• Nanotechnology
• Genetics
• Toxicology

Background:

• Silver nanoparticles (AgNPs) are widely used for their antimicrobial properties.
• The genotoxic effects of AgNPs on eukaryotic genomes are not fully understood.
• Schizosaccharomyces pombe shares significant gene homology with humans, making it a suitable model organism.

Purpose of the Study:

• To evaluate the mutagenic effects of AgNPs on the eukaryotic fission yeast, Schizosaccharomyces pombe.
• To determine the impact of AgNPs on genome-wide mutation rates and types.
• To explore the mechanisms of AgNP-induced mutagenesis.

Main Methods:

• Utilized 283 mutation accumulation lines of S. pombe for approximately 260,000 cell divisions.
• Assessed mutations at single-nucleotide resolution and whole-genome scale.
• Employed RNA sequencing for differential gene-expression analysis to understand mutagenesis mechanisms.

Main Results:

• AgNP treatment increased the base-substitution mutation rate in S. pombe by 3.46× at four-fold degenerate sites.
• Small insertions and deletions (indels) occurred in non-simple sequence repeat regions.
• A significant increase in G:C → T:A transversions was observed, likely due to oxidative damage.

Conclusions:

• AgNPs exhibit genotoxicity in eukaryotic cells, increasing mutation rates.
• The observed increase in specific mutation types suggests oxidative damage as a potential mechanism.
• While potent antimicrobials, AgNPs may pose a low-magnitude genotoxic risk to eukaryotic and potentially human genomes.