Global DNA Adenine Methylation in Caenorhabditis elegans after Multigenerational Exposure to Silver Nanoparticles and Silver Nitrate

Multigenerational and transgenerational reproductive toxicity in a model nematode Caenorhabditis elegans has been shown previously after exposure to silver nanoparticles (Ag-NPs) and silver ions (AgNO(3)). However, there is a limited understanding on the transfer mechanism of the increased reproductive sensitivity to subsequent generations. This study examines changes in DNA methylation at epigenetic mark N6-methyl-2′-deoxyadenosine (6mdA) after multigenerational exposure of C. elegans to pristine and transformed-via-sulfidation Ag-NPs and AgNO(3). Levels of 6mdA were measured as 6mdA/dA ratios prior to C. elegans exposure (F(0)) after two generations of exposure (F(2)) and two generations of rescue (F(4)) using high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS). Although both AgNO(3) and Ag-NPs induced multigenerational reproductive toxicity, only AgNO(3) exposure caused a significant increase in global 6mdA levels after exposures (F(2)). However, after two generations of rescue (F(4)), the 6mdA levels in AgNO(3) treatment returned to F(0) levels, suggesting other epigenetic modifications may be also involved. No significant changes in global DNA methylation levels were observed after exposure to pristine and sulfidized sAg-NPs. This study demonstrates the involvement of an epigenetic mark in AgNO(3) reproductive toxicity and suggests that AgNO(3) and Ag-NPs may have different toxicity mechanisms.