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.
Highlights
In recent years, nanotechnology has brought a lot of improvements and advances in the treatment and diagnosis of diseases due to the development of improved contrast agents [1,2], and drug delivery vehicles [3,4,5] using nanomaterials
Immunocytochemistry staining (Figure 1A) shows that c-Jun was significantly translocated into the nuclei in cells after 24 h treatment with metallic nickel nano- or fine particles compared to control
Numerous studies have documented the carcinogenicity of nickel compounds [7,8,9], but the carcinogenic effect of metallic nickel remains to be clarified
Summary
Nanotechnology has brought a lot of improvements and advances in the treatment and diagnosis of diseases due to the development of improved contrast agents [1,2], and drug delivery vehicles [3,4,5] using nanomaterials. The use of metallic nanoparticles and their compounds have been paramount in such advances. While many studies have been published on the carcinogenicity of nickel compounds [7,8,9], the carcinogenicity of metallic nickel is still uncertain [10,11,12]. In vivo experiments and epidemiology studies show that nickel compounds are carcinogenic [13]. Nickel compounds are classified by the International Agency for Research on Cancer (IARC) as carcinogens to human being [14]. Though the epidemiological studies on the carcinogenicity metallic nickel are not conclusive [15], experimental animal studies suggest that metallic nickel nanoparticles may be carcinogenic [10]. Nickel nanoparticles are widely used in industry due to its unique characteristics with production estimated to be around 20 tons per year in the United
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