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Metallic nickel nanoparticles may exhibit higher carcinogenic potential than fine particles in JB6 cells.

Abstract
While numerous studies have described the pathogenic and carcinogenic effects of nickel compounds, little has been done on the biological effects of metallic nickel. Moreover, the carcinogenetic potential of metallic nickel nanoparticles is unknown. Activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) have been shown to play pivotal roles in tumor initiation, promotion, and progression. Mutation of the p53 tumor suppressor gene is considered to be one of the steps leading to the neoplastic state. The present study examines effects of metallic nickel fine and nanoparticles on tumor promoter or suppressor gene expressions as well as on cell transformation in JB6 cells. Our results demonstrate that metallic nickel nanoparticles caused higher activation of AP-1 and NF-κB, and a greater decrease of p53 transcription activity than fine particles. Western blot indicates that metallic nickel nanoparticles induced a higher level of protein expressions for R-Ras, c-myc, C-Jun, p65, and p50 in a time-dependent manner. In addition, both metallic nickel nano- and fine particles increased anchorage-independent colony formation in JB6 P+ cells in the soft agar assay. These results imply that metallic nickel fine and nanoparticles are both carcinogenetic in vitro in JB6 cells. Moreover, metallic nickel nanoparticles may exhibit higher carcinogenic potential, which suggests that precautionary measures should be taken in the use of nickel nanoparticles or its compounds in nanomedicine.
AuthorsRuth Magaye, Qi Zhou, Linda Bowman, Baobo Zou, Guochuan Mao, Jin Xu, Vincent Castranova, Jinshun Zhao, Min Ding
JournalPloS one (PLoS One) Vol. 9 Issue 4 Pg. e92418 ( 2014) ISSN: 1932-6203 [Electronic] United States
PMID24691273 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Carcinogens
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Particulate Matter
  • Proto-Oncogene Proteins c-jun
  • Transcription Factor AP-1
  • Transcription Factor RelA
  • Tumor Suppressor Protein p53
  • Nickel
Topics
  • Animals
  • Carcinogens (toxicity)
  • Cell Adhesion (drug effects)
  • Cell Line
  • Cell Nucleus (drug effects, metabolism)
  • Colony-Forming Units Assay
  • Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
  • Metal Nanoparticles (toxicity)
  • Mice
  • Nickel (toxicity)
  • Particle Size
  • Particulate Matter (toxicity)
  • Protein Transport (drug effects)
  • Proto-Oncogene Proteins c-jun (metabolism)
  • Surface Properties
  • Transcription Factor AP-1 (metabolism)
  • Transcription Factor RelA (metabolism)
  • Transcription, Genetic (drug effects)
  • Tumor Suppressor Protein p53 (genetics, metabolism)

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