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Cadmium and Its Impact on Genomic Stability

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Cadmium Interaction with Animal Cells

Abstract

The carcinogenicity of cadmium for humans and experimental animals has been long established, most evident for tumors in the lung and kidney, but with increasing evidence also for other tumor locations. While cadmium does not interact directly with DNA, elevated levels of reactive oxygen species (ROS), the interference with the cellular response to DNA damage including all major DNA repair systems as well as the inactivation of tumor suppressor functions appear to be of major importance, thereby increasing the susceptibility towards exogenous and endogenous DNA damage. Furthermore, the deregulation of cell growth, the resistance to apoptosis, as well as epigenetic alterations have been demonstrated in diverse experimental systems. Particularly sensitive targets appear to be proteins with zinc-binding structures, present in many DNA repair proteins, transcription factors and in the tumor suppressor protein p53. The interaction with critical thiol groups and/or the enhanced generation of ROS may also provoke an interference with cellular redox regulation of critical signaling pathways. Especially the combination of these multiple mechanisms may give rise to a high degree of genomic instability in cadmium-adapted cells, relevant not only for tumor initiation but also for later steps in tumor development.

This chapter has been partly adapted with permission from Ref. [1].

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Authors and Affiliations

  1. Food Chemistry and Toxicology, Karlsruhe Institute of Technology (KIT), 76131, Karlsruhe, Germany

    Andrea Hartwig

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  1. Andrea Hartwig
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Correspondence to Andrea Hartwig .

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Editors and Affiliations

  1. Department of Physiology, Pathophysiology & Toxicology and ZBAF, Faculty of Health, School of Medicine, Witten/Herdecke University, Witten, Germany

    Frank Thévenod

  2. Department of Chemistry and Biochemistry, University of Wisconsin–Milwaukee, Milwaukee, WI, USA

    David Petering

  3. Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

    Douglas M. Templeton

  4. Department of Physiology, Pathophysiology & Toxicology and ZBAF, Faculty of Health, School of Medicine, Witten/Herdecke University, Witten, Germany

    Wing-Kee Lee

  5. Department of Food Chemistry and Toxicology, Institute for Applied Biosciences, KIT, Karlsruhe, Baden-Württemberg, Germany

    Andrea Hartwig

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Hartwig, A. (2018). Cadmium and Its Impact on Genomic Stability. In: Thévenod, F., Petering, D., M. Templeton, D., Lee, WK., Hartwig, A. (eds) Cadmium Interaction with Animal Cells. Springer, Cham. https://doi.org/10.1007/978-3-319-89623-6_5

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