title: 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.
authors.affiliation: Public Health Department of Medical School, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Ruth
authors.initials: R
authors.lastname: Magaye
authors.affiliation: Public Health Department of Medical School, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States of America.
authors.forename: Linda
authors.initials: L
authors.lastname: Bowman
authors.affiliation: Public Health Department of Medical School, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Baobo
authors.initials: B
authors.lastname: Zou
authors.affiliation: Public Health Department of Medical School, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Guochuan
authors.initials: G
authors.lastname: Mao
authors.affiliation: Public Health Department of Medical School, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States of America.
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
authors.affiliation: Public Health Department of Medical School, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China; Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States of America.
authors.forename: Jinshun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States of America.
authors.forename: Min
authors.initials: M
authors.lastname: Ding
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003114:Colony-Forming Units Assay; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D009532:Nickel / Q000633:toxicity*; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D021381:Protein Transport / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D013499:Surface Properties; D018808:Transcription Factor AP-1 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D002273:Carcinogens; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D052638:Particulate Matter; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; D009532:Nickel