||I U P A C
Organizations & People
Pure Appl. Chem. Vol.
72, No. 6, pp. 1007-1014, 2000
Recent advances in metal carcinogenicity*
University of Karlsruhe, Department of Food Chemistry,
Postfach 6980, D 76128 Karlsruhe, Germany
Abstract: The carcinogenicity of nickel, chromium, arsenic,
cobalt, and cadmium compounds has long been recognized. Nevertheless,
the mechanisms involved in tumor formation are not well understood.
The carcinogenic potential depends on metal species; major determinants
are oxidation state and solubility. Two modes of action seem to be predominant:
the induction of oxidative DNA damage and the interaction with DNA repair
processes, leading to an enhancement of genotoxicity in combination
with a variety of DNA-damaging agents. Nucleotide excision repair (NER)
is inhibited at low, non-cytotoxic concentrations of nickel(II), cadmium(II),
cobalt(II), and arsenic(III); the repair of oxidative DNA base modifications
is disturbed by nickel(II) and cadmium(II). One reason for repair inhibition
appears to be the displacement of zinc(II) and magnesium(II). Potentially
sensitive targets are so-called zinc finger structures present in several
DNA repair enzymes such as the mammalian XPA protein and the bacterial
formamidopyrimidine-DNA glycosylase (Fpg protein); detailed studies
revealed that each zinc finger protein exerts unique sensitivities toward
toxic metal ions. Taken together, toxic metal ions may lower the genetic
stability by inducing oxidative DNA damage and by decreasing the repair
capacity towards DNA lesions induced by endogenous and exogenous mutagens,
which may in turn increase the risk of tumor formation.
at the 4th Congress of Toxicology in Developing Countries (4th CTOX-DC),
Antalya, Turkey, 6-10 November 1999
Back to Contents for access to full
Page last modified 13 September
Copyright © 2000 International Union of Pure and Applied Chemistry.
Questions or comments about IUPAC, please contact, the Secretariat.
Questions regarding the website, please contact web