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

Anye Wamucho, Jason Unrine, John May, Olga Tsyusko

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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 (AgNO3). 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 AgNO3. Levels of 6mdA were measured as 6mdA/dA ratios prior to C. elegans exposure (F0) after two generations of exposure (F2) and two generations of rescue (F4) using high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS). Although both AgNO3 and Ag-NPs induced multigenerational reproductive toxicity, only AgNO3 exposure caused a significant increase in global 6mdA levels after exposures (F2). However, after two generations of rescue (F4), the 6mdA levels in AgNO3 treatment returned to F0 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 AgNO3 reproductive toxicity and suggests that AgNO3 and Ag-NPs may have different toxicity mechanisms.

Original languageEnglish
Article number6168
JournalInternational Journal of Molecular Sciences
Issue number7
StatePublished - Apr 2023

Bibliographical note

Funding Information:
This research was funded by the U.S. National Science Foundation (NSF) under EF-0830093, DBI-1266252, CBET-1530594, and ECO-CBET 2133568. Partial support was also provided by the United States Department of Agriculture National Institute of Food and Agriculture (NIFA) multistate project NC1194 (O.T.). The Caenorhabditis Genetics Center CGC) is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440).

Publisher Copyright:
© 2023 by the authors.


  • adenine modifications
  • demethylase
  • epigenetics
  • gene expression
  • methyltransferase
  • nanomaterials
  • nematode

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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