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.