title: Effect of particle size and dispersion status on cytotoxicity and genotoxicity of zinc oxide in human bronchial epithelial cells.
abstract: Data available on the genotoxicity of zinc oxide (ZnO) nanoparticles (NPs) are controversial. Here, we examined the effects of particle size and dispersion status on the cytotoxicity and genotoxicity of nanosized and fine ZnO, in the presence and absence of bovine serum albumin (BSA; 0.06%) in human bronchial epithelial BEAS-2B cells. Dynamic light scattering analysis showed the most homogenous dispersions in water alone for nanosized ZnO and in water with BSA for fine ZnO. After a 48-h treatment, both types of ZnO were cytotoxic within a similar, narrow dose range (1.5-3.0μg/cm(2)) and induced micronuclei at a near toxic dose range (1.25-1.75μg/cm(2)), both with and without BSA. In the comet assay, nanosized ZnO (1.25-1.5μg/cm(2)), in the absence of BSA, caused a statistically significant increase in DNA damage after 3-h and 6-h treatments, while fine ZnO did not. Our findings may be explained by better uptake or faster intracellular dissolution of nanosized ZnO without BSA during short treatments (3-6h; the comet assay), with less differences between the two ZnO forms after longer treatments (>48h; the in vitro micronucleus test). As ZnO is genotoxic within a narrow dose range partly overlapping with cytotoxic doses, small experimental differences e.g. in the dispersion of ZnO particles may have a substantial effect on the genotoxicity of the nominal doses added to the cell culture.
authors.affiliation: Finnish Institute of Occupational Health, FI-00251 Helsinki, Finland; Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 91-348 Łódź, Poland. Electronic address: joanna@imp.lodz.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Roszak
authors.affiliation: Finnish Institute of Occupational Health, FI-00251 Helsinki, Finland; Department of Anatomy, Embryology and Genetics, University of Zaragoza, 50013 Zaragoza, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Catalán
authors.affiliation: Finnish Institute of Occupational Health, FI-00251 Helsinki, Finland.
authors.forename: Hilkka
authors.initials: H
authors.lastname: Järventaus
authors.affiliation: Finnish Institute of Occupational Health, FI-00251 Helsinki, Finland.
authors.forename: Hanna K
authors.initials: HK
authors.lastname: Lindberg
authors.affiliation: Finnish Institute of Occupational Health, FI-00251 Helsinki, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Suhonen
authors.affiliation: Finnish Institute of Occupational Health, FI-00251 Helsinki, Finland; Department of Materials Science, Tampere University of Technology, FI-33101 Tampere, Finland.
authors.forename: Minnamari
authors.initials: M
authors.lastname: Vippola
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 91-348 Łódź, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Stępnik
authors.affiliation: Finnish Institute of Occupational Health, FI-00251 Helsinki, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Norppa
mesh_terms: D000818:Animals; D001980:Bronchi / Q000166:cytology*; D002417:Cattle; D002460:Cell Line; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D015162:Micronucleus Tests; D010316:Particle Size; D012710:Serum Albumin, Bovine / Q000737:chemistry; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: D012710:Serum Albumin, Bovine; D015034:Zinc Oxide
keywords: DNA damage; Genotoxicity; Micronucleus; Nanoparticle; Zinc oxide