title: Contribution of ionic silver to genotoxic potential of nanosilver in human liver HepG2 and colon Caco2 cells evaluated by the cytokinesis-block micronucleus assay.
abstract: Extensive human exposure to food- and cosmetics-related consumer products containing nanosilver is of public concern because of the lack of information about their safety. Genotoxicity is an important endpoint for the safety and health hazard assessment of regulated products including nanomaterials. The in vitro cytokinesis-block micronucleus (CBMN) assay is a very useful test for predictive genotoxicity testing. Recently, we have reported the genotoxicity of 20 nm nanosilver in human liver HepG2 and colon Caco2 cells evaluated using the CBMN assay. The objective of our present study was three-fold: (i) to evaluate if HepG2 and Caco2 cells are valuable in vitro models for rapid genotoxicity screening of nanosilver; (ii) to test the hypothesis that the nanoparticle size and cell types are critical determinants of its genotoxicity; and (iii) to determine if ionic silver contributes to the nanosilver genotoxicity. With these objectives in mind, we evaluated the genotoxic potential of 50 nm nanosilver of the same shape, composition, surface charge, obtained from the same commercial source, under the same experimental conditions and the same genotoxic CBMN endpoint used for the previously tested 20 nm silver. The ionic silver (silver acetate) was also evaluated under the same conditions. Results of our study show that up to the concentrations tested in these cell types, the smaller (20 nm) nanosilver induces micronucleus formation in both the cell types but the larger (50 nm) nanosilver and the ionic silver provide a much weaker response compared with controls under the same conditions.
authors.affiliation: Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, U. S. Food and Drug Administration, Laurel, MD, 20708, USA.
authors.forename: Saura C
authors.initials: SC
authors.lastname: Sahu
authors.affiliation: Bioreliance Corporation, Rockville, MD, 20850, USA.
authors.forename: Shambhu
authors.initials: S
authors.lastname: Roy
authors.affiliation: Division of Chemistry and Material Sciences, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U. S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
authors.forename: Jiwen
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Division of Public Health Information and Analytics, Office of Analytics and Outreach, Center for Food Safety and Applied Nutrition, U. S. Food and Drug Administration, College Park, 20740, USA.
authors.forename: John
authors.initials: J
authors.lastname: Ihrie
mesh_terms: D018938:Caco-2 Cells; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D048749:Cytokinesis / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects*; D023381:Endpoint Determination; D056945:Hep G2 Cells; D006801:Humans; D016014:Linear Models; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D015162:Micronucleus Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity; D012834:Silver / Q000737:chemistry / Q000633:toxicity*
chemical_list: D009153:Mutagens; D012834:Silver
keywords: Caco2; HepG2; cytokinesis-block micronucleus; genotoxicity; in vitro micronucleus; micronucleus; nanoparticles; nanosilver; silver nanoparticles