Silver nanoparticles elevate mutagenesis of eukaryotic genomes

Metal nanoparticles, especially silver, have been used in various medical scenarios, due to their excellent antimicrobial effects. Recent studies have shown that AgNPs do not exert mutagenic effects on target bacteria, but the degree to which they compromise eukaryotic genomes remains unclear. To study this, we evaluated the mutagenic effects of AgNPs on the fission yeast Schizosaccharomyces pombe ATCC-16979, of which ∼23% genes are homologous to human ones, at single-nucleotide resolution, and whole-genome scale by running 283 mutation accumulation lines for ∼260, 000 cell divisions in total. We also explored the action and mutagenesis mechanisms using differential gene-expression analysis based on RNAseq. Upon AgNPs treatment, the genomic base-substitution mutation rate of S. pombe at four-fold degenerate sites increased by 3.46×, and small indels were prone to occur in genomic regions that are not simple sequence repeats. The G:C → T:A transversion rate was also significantly increased, likely mostly from oxidative damage. Thus, in addition to their antimicrobial potency, AgNPs might pose slight genotoxicity threats to eukaryotic and possibly human genomes, though at a low magnitude.