title: Differential cytotoxic and inflammatory potency of amorphous silicon dioxide nanoparticles of similar size in multiple cell lines.
abstract: The likelihood of environmental and health impacts of silicon dioxide nanoparticles (SiNPs) has risen, due to their increased use in products and applications. The biological potency of a set of similarly-sized amorphous SiNPs was investigated in a variety of cells to examine the influence of physico-chemical and biological factors on their toxicity. Cellular LDH and ATP, BrdU incorporation, resazurin reduction and cytokine release were measured in human epithelial A549, human THP-1 and mouse J774A.1 macrophage cells exposed for 24 h to suspensions of 5-15, 10-20 and 12 nm SiNPs and reference particles. The SiNPs were characterized in dry state and in suspension to determine their physico-chemical properties. The dose-response data were simplified into particle potency estimates to facilitate the comparison of multiple endpoints of biological effects in cells. Mouse macrophages were the most sensitive to SiNP exposures. Cytotoxicity of the individual cell lines was correlated while the cytokine responses differed, supported by cell type-specific differences in inflammation-associated pathways. SiNP (12 nm), the most cytotoxic and inflammogenic nanoparticle had the highest surface acidity, dry-state agglomerate size, the lowest trace metal and organics content, the smallest surface area and agglomerate size in suspension. Particle surface acidity appeared to be the most significant determinant of the overall biological activity of this set of nanoparticles. Combined with the nanoparticle characterization, integration of the biological potency estimates enabled a comprehensive determination of the cellular reactivity of the SiNPs. The approach shows promise as a useful tool for first-tier screening of SiNP toxicity.
authors.affiliation: a Environmental Health Science and Research Bureau, Health Canada, Tunney's Pasture , Ottawa , Canada.
authors.forename: Dalibor
authors.initials: D
authors.lastname: Breznan
authors.affiliation: a Environmental Health Science and Research Bureau, Health Canada, Tunney's Pasture , Ottawa , Canada.
authors.forename: Dharani D
authors.initials: DD
authors.lastname: Das
authors.affiliation: a Environmental Health Science and Research Bureau, Health Canada, Tunney's Pasture , Ottawa , Canada.
authors.forename: Julie S
authors.initials: JS
authors.lastname: O'Brien
authors.affiliation: a Environmental Health Science and Research Bureau, Health Canada, Tunney's Pasture , Ottawa , Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: MacKinnon-Roy
authors.affiliation: a Environmental Health Science and Research Bureau, Health Canada, Tunney's Pasture , Ottawa , Canada.
authors.forename: Surendra
authors.initials: S
authors.lastname: Nimesh
authors.affiliation: a Environmental Health Science and Research Bureau, Health Canada, Tunney's Pasture , Ottawa , Canada.
authors.forename: Ngoc Q
authors.initials: NQ
authors.lastname: Vuong
authors.affiliation: b New Substances Assessment and Control Bureau, Health Canada, Tunney's Pasture , Ottawa , Canada.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bernatchez
authors.affiliation: c Department of Earth and Environmental Sciences , University of Ottawa , Ottawa , Canada.
authors.forename: Nimal
authors.initials: N
authors.lastname: DeSilva
authors.affiliation: b New Substances Assessment and Control Bureau, Health Canada, Tunney's Pasture , Ottawa , Canada.
authors.forename: Myriam
authors.initials: M
authors.lastname: Hill
authors.affiliation: a Environmental Health Science and Research Bureau, Health Canada, Tunney's Pasture , Ottawa , Canada.
authors.forename: Prem
authors.initials: P
authors.lastname: Kumarathasan
authors.affiliation: a Environmental Health Science and Research Bureau, Health Canada, Tunney's Pasture , Ottawa , Canada.
authors.forename: Renaud
authors.initials: R
authors.lastname: Vincent
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D012822:Silicon Dioxide / Q000737:chemistry / Q000633:toxicity*; D013499:Surface Properties
chemical_list: D016207:Cytokines; D012822:Silicon Dioxide
keywords: Nanoparticles; cytokines; cytotoxicity; pathway analysis; silica