title: In vitro assessment of engineered nanomaterials using a hepatocyte cell line: cytotoxicity, pro-inflammatory cytokines and functional markers.
abstract: Effects on the liver C3A cell line treated with a panel of engineered nanomaterials (NMs) consisting of two zinc oxide particles (ZnO; coated 100 nm and uncoated 130 nm), two multi-walled carbon nanotubes (MWCNTs), one silver (Ag < 20 nm), one 7 nm anatase, two rutile TiO2 nanoparticles (10 and 94 nm) and two derivatives with positive and negative covalent functionalisation of the 10 nm rutile were evaluated. The silver particles elicited the greatest level of cytotoxicity (24 h LC50 - 2 µg/cm(2)). The silver was followed by the uncoated ZnO (24 h LC50 - 7.5 µg/cm(2)) and coated ZnO (24 h LC50 - 15 µg/cm(2)) particles with respect to cytotoxicity. The ZnO NMs were found to be about 50-60% soluble which could account for their toxicity. By contrast, the Ag was <1% soluble. The LC50 was not attained in the presence of any of the other engineered NMs (up to 80 µg/cm(2)). All NMs significantly increased IL-8 production. Meanwhile, no significant change in TNF-α, IL-6 or CRP was detected. Urea and albumin production were measured as indicators of hepatic function. These markers were only altered by the coated and uncoated ZnO, which significantly decreased albumin production.
authors.affiliation: Heriot-Watt University, School of Life Sciences, John Muir Building, Edinburgh, UK. Ak435@hw.ac.uk
authors.forename: Ali
authors.initials: A
authors.lastname: Kermanizadeh
authors.forename: Giulio
authors.initials: G
authors.lastname: Pojana
authors.forename: Birgit K
authors.initials: BK
authors.lastname: Gaiser
authors.forename: Renie
authors.initials: R
authors.lastname: Birkedal
authors.forename: Dagmar
authors.initials: D
authors.lastname: Bilanicová
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.forename: Keld Alstrup
authors.initials: KA
authors.lastname: Jensen
authors.forename: Börje
authors.initials: B
authors.lastname: Sellergren
authors.forename: Gary R
authors.initials: GR
authors.lastname: Hutchison
authors.forename: Antonio
authors.initials: A
authors.lastname: Marcomini
authors.forename: Vicki
authors.initials: V
authors.lastname: Stone
mesh_terms: D000418:Albumins / Q000378:metabolism; D000704:Analysis of Variance; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D049329:Nanostructures / Q000633:toxicity*; D012834:Silver / Q000633:toxicity; D014025:Titanium / Q000633:toxicity; D014508:Urea / Q000378:metabolism; D015034:Zinc Oxide / Q000633:toxicity
chemical_list: D000418:Albumins; D015415:Biomarkers; D016207:Cytokines; C009495:titanium dioxide; D012834:Silver; D014508:Urea; D014025:Titanium; D015034:Zinc Oxide