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

Multigenerational and transgenerational reproductive toxicity in a model nematode has been shown previously after exposure to silver nanoparticles (Ag-NPs) and silver ions (AgNO). 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 to pristine and transformed-via-sulfidation Ag-NPs and AgNO. Levels of 6mdA were measured as 6mdA/dA ratios prior to exposure (F) after two generations of exposure (F) and two generations of rescue (F) using high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS). Although both AgNO and Ag-NPs induced multigenerational reproductive toxicity, only AgNO exposure caused a significant increase in global 6mdA levels after exposures (F). However, after two generations of rescue (F), the 6mdA levels in AgNO treatment returned to F 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 reproductive toxicity and suggests that AgNO and Ag-NPs may have different toxicity mechanisms.