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Minimal influence of metallothionein over-expression on nickel carcinogenesis in mice

  1. Author:
    Waalkes, M. P.
    Liu, J.
    Kasprzak, K. S.
    Diwan, B. A.

  2. Author Address

    NCI, Comparat Carcinogenesis Lab, Inorgan Carcinogenesis Sect, NIEHS,NIH, Res Triangle Pk, NC 27709 USA. NCI, Comparat Carcinogenesis Lab, Metals Sect, Ft Detrick, MD 21702 USA. NCI, SAIC Frederick, Intramurla Res Support Program, Ft Detrick, MD 21702 USA Waalkes, MP, NCI, Comparat Carcinogenesis Lab, Inorgan Carcinogenesis Sect, NIEHS,NIH, 111 Alexander Dr,POB 12233,MD F0-09, Res Triangle Pk, NC 27709 USA
    1. Year: 2004
    2. Date: NOV 28
  2. Journal: Toxicology Letters
    1. 153
    2. 3
    3. Pages: 357-364
  4. Type of Article: Article
  1. Abstract:

    Metallothionein (MT) is a metal-binding protein associated with tolerance to metals and oxidative stress. Nickel is a metal carcinogen potentially acting through oxidative attack on critical biomolecules. We investigated the role of NIT in nickel carcinogenesis using MT-transgenic mice that constitutively over-express MT-I in all tissues tested. Groups of 25 male MT-transgenic and wild type (C57BL/6; WT) mice received intramuscular injections of nickel subsulfide (Ni3S2) in both thighs at doses of 0 (control), 0.5, or 1.0 mg/site at 12 weeks of age and were observed for 104 weeks. Injection site tumors (ISTs; primarily fibrosarcomas) started occurring 45 weeks after nickel injection and IST incidence was similar in the WT (control - 0%, 0.5 mg/site 20%, 1.0 mg/site - 40%) and NIT-transgenic mice (control - 0%, 0.5 mg/site - 28%, 1.0 mg/site - 29%). At the 0.5 mg/site dose the average time to IST in MT-transgenic mice was similar to13 weeks shorter than in WT mice. Spontaneous lung tumors developed in 25% of control WT mice but none developed in control MT-transgenic mice. A nickel dose-related trend for increased lung tumors occurred in MT-transgenic mice but not in WT mice. Thus, the over-expression of NIT did not significantly mitigate the carcinogenic response to nickel. Published by Elsevier Ireland Ltd

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External Sources

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  2. DOI: 10.1016/j.toxlet.2004.06.003
  3. View record in Web of Science®
  4. WOS: 000224713400007

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