The Oxidative Damage Hypothesis of Metal-Induced Genotoxicity and Carcinogenesis

  • K. S. Kasprzak
Part of the NATO ASI Series book series (ASEN2, volume 26)


This paper presents evidence that genotoxic and carcinogenic effects of certain transition metals are associated with oxidative damage to DNA and nuclear proteins. The metals, including Ni, Cr, and Co, are capable of causing promutagenic lesions, such as DNA base modifications, inter- and intra-molecular crosslinks of DNA and proteins, DNA strand breaks, rearrangements, and depurination. The underlying mechanisms involve generation of various kinds of active oxygen and other highly reactive species from metal-catalyzed redox reactions of O2, H2O2, lipid peroxides, and other cellular substrates, and their attack on cell nucleus. Metal-mediated damage of other tissue and cellular components, resulting in inflammation, lipid peroxidation, suppression of cellular antioxidant defenses, and impairment of DNA repair, may also contribute to those mechanisms. Data revealing the oxidative character of metal-induced promutagenic DNA damage are particularly strong for two most powerful human metal carcinogens, nickel and chromium. However, without excluding various pathogenic effects caused by non-redox interactions, oxidative damage tends to take the leading role in explaining the mechanisms of carcinogenicity of cobalt and certain other metals as well.


Acute Intermittent Porphyria Carcinogenic Metal Thymine Glycol Ferric Nitrilotriacetate Metal Carcinogenesis 
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Copyright information

© Springer Science+Business Media Dordrecht 1997

Authors and Affiliations

  • K. S. Kasprzak
    • 1
  1. 1.Laboratory of Comparative CarcinogenesisNational Cancer Institute, FCRDCFrederickUSA

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