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Induction of oxidative DNA damage by carcinogenic metals

  1. Author:
    Bal, W.
    Kasprzak, K. S.

  2. Author Address

    Univ Wroclaw, Fac Chem, Ul F Joliot Curie 14, PL-50383 Wroclaw, Poland Univ Wroclaw, Fac Chem, PL-50383 Wroclaw, Poland Polish Acad Sci, Inst Biochem & Biophys, PL-02532 Warsaw, Poland NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA Bal W Univ Wroclaw, Fac Chem, Ul F Joliot Curie 14, PL-50383 Wroclaw, Poland
    1. Year: 2002
  2. Journal: Toxicology Letters
    1. 127
    2. 1-3
    3. Pages: 55-62
  4. Type of Article: Article
  1. Abstract:

    The metal ions carcinogenic to humans are As, Be, Cd, Cr and Ni, and the candidates also include Co, Cu, Fe and Pt. A range of molecular mechanisms was proposed for these metals, reflecting their diverse chemical properties. The oxidative concept in metal carcinogenesis proposes that some complexes of the above metals (Co, Cr, Cu, Fe, Ni) formed in vivo undergo redox cycling, yielding reactive oxygen species and/or high valence metal ions which oxidize DNA. Some of the products of oxidative DNA damage, including 8-oxoguanine and strand breaks, induce mutations, which may lead to neoplastic transformation. The establishment of metal-binding modes in the cell nucleus and of their reactivity is crucial for the understanding of molecular events in metal carcinogenesis. We have proposed the binding sites for Ni(II) and Cu(II) in core histones (H3, H2A) and sperm protamines (HP2) and, using molecular models, provided evidence for the generation of promutagenic oxidative DNA damage by the bound metals. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

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