title: In vitro and in vivo evaluation of the toxicities induced by metallic nickel nano and fine particles.
abstract: Nickel nanoparticles (Ni NPs) have been applied in various fields along with the rapid development of nanotechnology. However, the potential adverse health effects of the Ni NPs are unclear. To investigate the cyto- and genotoxicity and compare the differences between the Ni NPs and the nickel fine particles (Ni FPs), Sprague-Dawley (SD) rats and A549 cells were treated with different doses of Ni NPs or FPs. Intra-tracheal instillation of Ni NPs and FPs caused acute toxicity in the lungs, liver and kidneys of the SD rats. Even though the histology of the lungs showed hyperplastic changes and the protein expression of HO-1 and Nrf2 detected by western blot showed lung burden overload, no significant increase was observed to the expression level of oncoprotein C-myc. The results from cell titer-Glo assay and comet assay indicated that Ni NPs were more potent in causing cell toxicity and genotoxicity in vitro than Ni FPs. In addition, Ni NPs increased the expression of C-myc in vitro, but these increases may not have been due to oxidative stress since no significant dose-dependent changes were seen in HO-1 and Nrf2 expressions. Although Ni NPs have the potential to cause DNA damage in A549 cells in vitro, the molecular mechanisms that led to these changes and their tumorigenic potential is still debatable. In short, Ni NPs were more potent in causing cell toxicity and genotoxicity in vitro than Ni FPs, and intra-tracheal instillation of Ni NPs and FPs caused toxicity in organs of the SD rats, while it showed similar to the effects for both particle types. These results suggested that both Ni NPs and FPs have the potential to be harmful to human health, and Ni NPs may have higher cyto- and genotoxic effects than Ni FPs under the same treatment dose.
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medicine School of Ningbo University, 818 Fenghua Road, Jiangbei District, Ningbo, 315211, China.
authors.forename: Ruth
authors.initials: R
authors.lastname: Magaye
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medicine School of Ningbo University, 818 Fenghua Road, Jiangbei District, Ningbo, 315211, China.
authors.forename: Yuanliang
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medicine School of Ningbo University, 818 Fenghua Road, Jiangbei District, Ningbo, 315211, China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medicine School of Ningbo University, 818 Fenghua Road, Jiangbei District, Ningbo, 315211, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medicine School of Ningbo University, 818 Fenghua Road, Jiangbei District, Ningbo, 315211, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medicine School of Ningbo University, 818 Fenghua Road, Jiangbei District, Ningbo, 315211, China.
authors.forename: Guochuan
authors.initials: G
authors.lastname: Mao
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medicine School of Ningbo University, 818 Fenghua Road, Jiangbei District, Ningbo, 315211, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medicine School of Ningbo University, 818 Fenghua Road, Jiangbei District, Ningbo, 315211, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Yue
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medicine School of Ningbo University, 818 Fenghua Road, Jiangbei District, Ningbo, 315211, China.
authors.forename: Baobo
authors.initials: B
authors.lastname: Zou
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medicine School of Ningbo University, 818 Fenghua Road, Jiangbei District, Ningbo, 315211, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medicine School of Ningbo University, 818 Fenghua Road, Jiangbei District, Ningbo, 315211, China. zhaojinshun@nbu.edu.cn.
authors.forename: Jinshun
authors.identifier: http://orcid.org/0000-0001-6012-1611
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000818:Animals; D015415:Biomarkers; D001706:Biopsy; D002460:Cell Line; D002470:Cell Survival; D020552:Comet Assay; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D009532:Nickel / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D051381:Rats; D018675:Toxicity Tests
chemical_list: D015415:Biomarkers; D009532:Nickel
keywords: Carcinogenicity; Cytotoxicity; Fine particles; Genotoxicity; Nanoparticles; Nickel