INVESTIGATION OF SIZE-DEPENDANT GENOTOXICITY OF SILVER NANOPARTICLES IN MULTIPLE BIOLOGICAL MODELS
Bryce Marquis1, Li Komatsu2, Shyam Nathan3, Monique Johnson4, Lee Yu1, and Bryant Nelson1
1National Institute of Standards and Technology
2Food and Drug Administration
3 Georgetown University, Department of Biotechnology
4University of Massachusetts Amherst, Department of Chemistry
The increased incorporation of engineered nanomaterials into consumer goods has led to increased need for toxicological information about these materials. Silver nanomaterials are widely used due to their antibacterial properties, but the mechanism of their antimicrobial activity is widely unknown. It is suspected that the release of ionic silver species from the nanoparticle is involved in their toxicity. In these studies, silver nanomaterials with different nominal sizes (10 nm-100 nm) and silver ions were incubated with both acellular and in vivo biological models in order to investigate their genotoxicity. After exposure, oxidized DNA lesions (such as 8-hydroxy-guanine, Fapy adenine, and thymine glycol) were identified and quantified using chromatographic separation with isotope dilution mass spectrometry detection. In acellular studies, silver nanoparticles of varied size were incubated with calf-thymus DNA and size-dependant increases in oxidative DNA damage were observed. The roles of solution pH, temperature and light were investigated in this observed damage.† In vivo studies used the same size panel of nanoparticles to expose a nematode model, C. elegans, to nanoparticles. Elemental analysis found increased nanoparticle uptake with increasing particle size suggesting the C. eleganís size-dependant procorpus filtration mechanism plays an important role in nanomaterial uptake. However, increased genotoxicity was observed with decreasing particle size suggesting the dissolution of silver may play a prominent role in this DNA damage. Future studies will explore the effects of nanoparticle agglomeration state on the observed uptake and genotoxicity.