Carcinogenicity of metal compounds: possible role of DNA repair inhibition

Compounds of chromium, nickel, cadmium, cobalt and arsenic are well-known carcinogens. However, their mode of action is still not fully understood, since, with the exception of chromium(VI), direct genotoxic effects are rather weak and/or restricted to comparatively high concentrations. However, current evidence suggests that DNA repair systems are very sensitive targets for nickel(II), cadmium(II), cobalt(II) and arsenic(III), leading to a diminished removal of endogenous DNA lesions and of DNA damage induced by environmental agents, which in turn may increase the risk of tumor formation. Nevertheless, the underlying mechanisms are quite different, depending for example on the ability of toxic metal ions to compete with magnesium ions or to displace zinc ions in zinc finger structures of DNA repair enzymes. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.