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Bioavailability, intracellular mobilization of nickel, and HIF-1α activation in human lung epithelial cells exposed to metallic nickel and nickel oxide nanoparticles.
- Source :
-
Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2011 Nov; Vol. 124 (1), pp. 138-48. Date of Electronic Publication: 2011 Aug 09. - Publication Year :
- 2011
-
Abstract
- Micron-sized particles of poorly soluble nickel compounds, but not metallic nickel, are established human and rodent carcinogens. In contrast, little is known about the toxic effects of a growing number of Ni-containing materials in the nano-sized range. Here, we performed physicochemical characterization of NiO and metallic Ni nanoparticles and examined their metal ion bioavailability and toxicological properties in human lung epithelial cells. Cellular uptake of metallic Ni and NiO nanoparticles, but not metallic Ni microparticles, was associated with the release of Ni(II) ions after 24-48 h as determined by Newport Green fluorescence. Similar to soluble NiCl₂, NiO nanoparticles induced stabilization and nuclear translocation of hypoxia-inducible factor 1α (HIF-1α) transcription factor followed by upregulation of its target NRDG1 (Cap43). In contrast to no response to metallic Ni microparticles, nickel nanoparticles caused a rapid and prolonged activation of the HIF-1α pathway that was stronger than that induced by soluble Ni(II). Soluble NiCl₂ and NiO nanoparticles were equally toxic to H460 human lung epithelial cells and primary human bronchial epithelial cells; metallic Ni nanoparticles showed lower toxicity and Ni microparticles were nontoxic. Cytotoxicity induced by all forms of Ni occurred concomitant with activation of an apoptotic response, as determined by dose- and time-dependent cleavage of caspases and poly (ADP-ribose) polymerase. Our results show that metallic Ni nanoparticles, in contrast to micron-sized Ni particles, activate a toxicity pathway characteristic of carcinogenic Ni compounds. Moderate cytotoxicity and sustained activation of the HIF-1α pathway by metallic Ni nanoparticles could promote cell transformation and tumor progression.
- Subjects :
- Apoptosis drug effects
Biological Availability
Blotting, Western
Cell Line
Cell Survival drug effects
Epithelial Cells metabolism
Epithelial Cells ultrastructure
Humans
Lung cytology
Lung metabolism
Microscopy, Electron, Scanning
Microscopy, Electron, Transmission
Nanoparticles chemistry
Nickel administration & dosage
Nickel chemistry
Particle Size
Epithelial Cells drug effects
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Lung drug effects
Nanoparticles administration & dosage
Nickel pharmacokinetics
Nickel toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0929
- Volume :
- 124
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Toxicological sciences : an official journal of the Society of Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 21828359
- Full Text :
- https://doi.org/10.1093/toxsci/kfr206