title: Responses of human cells to ZnO nanoparticles: a gene transcription study.
abstract: The gene transcript profile responses to metal oxide nanoparticles was studied using human cell lines derived from the colon and skin tumors. Much of the research on nanoparticle toxicology has focused on models of inhalation and intact skin exposure, and effects of ingestion exposure and application to diseased skin are relatively unknown. Powders of nominally nanosized SiO2, TiO2, ZnO and Fe2O3 were chosen because these substances are widely used in consumer products. The four oxides were evaluated using colon-derived cell lines, RKO and CaCo-2, and ZnO and TiO2 were evaluated further using skin-derived cell lines HaCaT and SK Mel-28. ZnO induced the most notable gene transcription changes, even though this material was applied at the lowest concentration. Nano-sized and conventional ZnO induced similar responses suggesting common mechanisms of action. The results showed neither a non-specific response pattern common to all substances nor synergy of the particles with TNF-α cotreatment. The response to ZnO was not consistent with a pronounced proinflammatory signature, but involved changes in metal metabolism, chaperonin proteins, and protein folding genes. This response was observed in all cell lines when ZnO was in contact with the human cells. When the cells were exposed to soluble Zn, the genes involved in metal metabolism were induced but the genes involved in protein refoldling were unaffected. This provides some of the first data on the effects of commercial metal oxide nanoparticles on human colon-derived and skin-derived cells.
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, 30 S. 2000 East, Salt Lake City, Utah 84112, USA. philip.moos@utah.edu
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Moos
authors.forename: Kyle
authors.initials: K
authors.lastname: Olszewski
authors.forename: Matthew
authors.initials: M
authors.lastname: Honeggar
authors.forename: Pamela
authors.initials: P
authors.lastname: Cassidy
authors.forename: Sancy
authors.initials: S
authors.lastname: Leachman
authors.forename: David
authors.initials: D
authors.lastname: Woessner
authors.forename: N Shane
authors.initials: NS
authors.lastname: Cutler
authors.forename: John M
authors.initials: JM
authors.lastname: Veranth
mesh_terms: D002460:Cell Line / Q000187:drug effects* / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D046228:Microarray Analysis; D010316:Particle Size; D014158:Transcription, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015034:Zinc Oxide / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D015034:Zinc Oxide