title: Iron oxide nanoparticle toxicity testing using high-throughput analysis and high-content imaging.
abstract: Applying validated in vitro assays to the study of nanoparticle toxicity is a growing trend in nanomaterial risk assessment. Precise characterisation of reference nanomaterials and a well-regulated in vitro testing system are required to determine the physicochemical descriptors which dictate the toxic potential of nanoparticles. The use of automated, high-throughput technologies to facilitate the identification and prioritisation of nanomaterials which could pose a risk is desirable and developments are underway. In this study, two mammalian fibroblast lines (Balb/c 3T3 and COS-1 cells) were treated with a range of concentrations of iron oxide nanomaterials manufactured for use in medical diagnostics, using an automated platform and high-content-imaging endpoints for cell viability, oxidative stress and DNA damage (double-strand breaks). At the same time, the high-throughput comet assay was employed to measure DNA strand breaks and oxidised bases. Our results show that these methods provide a fast way to determine the toxicity of coated and uncoated iron oxide nanoparticles and, furthermore, to predict the mechanism of toxicity in vitro.
authors.affiliation: Institute for Health and Consumer Protection European Commission, Joint Research Centre , Ispra (VA) , Italy .
authors.forename: Georgina
authors.initials: G
authors.lastname: Harris
authors.forename: Taina
authors.initials: T
authors.lastname: Palosaari
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Magdolenova
authors.forename: Milena
authors.initials: M
authors.lastname: Mennecozzi
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Gineste
authors.forename: Luis
authors.initials: L
authors.lastname: Saavedra
authors.forename: Anne
authors.initials: A
authors.lastname: Milcamps
authors.forename: Anna
authors.initials: A
authors.lastname: Huk
authors.forename: Andrew Richard
authors.initials: AR
authors.lastname: Collins
authors.forename: Maria
authors.initials: M
authors.lastname: Dusinska
authors.forename: Maurice
authors.initials: M
authors.lastname: Whelan
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D020552:Comet Assay; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000633:toxicity*; D057166:High-Throughput Screening Assays / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000633:toxicity*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide
keywords: DNA damage; high-content imaging; high-throughput nanotoxicology; iron oxide nanoparticles; oxidative stress