Fresenius' Journal of Analytical Chemistry

, Volume 361, Issue 4, pp 377–380 | Cite as

Disruption of DNA repair processes by carcinogenic metal compounds

  • Andrea Hartwig
  • Leon Mullenders
  • Monika Asmuß
  • Heike Dally
  • M. Hartmann
Conference contribution

Abstract

Based on pronounced enhancing effects in combination with other DNA-damaging agents the potentials of Ni(II), Cd(II) and As(III) to interfere with DNA repair processes in HeLa cells was investigated. With respect to oxidative DNA damage, Ni(II) and Cd(II) induced DNA strand breaks starting at concentrations of 250 μM and 5 μM, respectively. The induction of oxidative DNA base modifications like 8-hydroxyguanine was restricted to the cytotoxic concentration of 750 μM Ni(II) and not observed after treatment with Cd(II). In contrast, the removal of oxidative DNA base modifications was inhibited at concentrations as low as 50 μM Ni(II) and 0.5 μM Cd(II). Regarding nucleotide excision repair, Ni(II) and Cd(II) disturbed the DNA-protein interactions involved in the damage recognition step when applying HeLa nuclear protein extracts and a UV-damaged oligonucleotide, while As(III) inhibited the actual incision event. In the case of Ni(II) and Cd(II), this effect was reversible by the addition of Mg(II) and Zn(II), respectively. Furthermore, Cd(II) inactivated the isolated bacterial Fpg protein, most likely by the displacement of Zn(II) from its zinc finger structure. Since DNA is continuously damaged by exogenous and endogenous sources, an impaired repair capacity might well account for the carcinogenic action of the metal compounds.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Andrea Hartwig
    • 1
  • Leon Mullenders
    • 2
  • Monika Asmuß
    • 1
  • Heike Dally
    • 1
  • M. Hartmann
    • 1
  1. 1.University of Bremen, Department of Biology and Chemistry, Postfach 330440, D-28334 Bremen, GermanyDE
  2. 2.Leiden University, Leiden, The NetherlandsNL

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