Carcinogenicity of metal compounds: possible role of DNA repair inhibition

Compounds of chromium, nickel, cadmium, cobalt and arsenic are well-known c arcinogens. However, their mode of action is still not fully understood, si nce, with the exception of chromium(VI), direct genotoxic effects are rathe r weak and/or restricted to comparatively high concentrations. However, cur rent evidence suggests that DNA repair systems are very sensitive targets f or nickel(II), cadmium(II), cobalt(II) and arsenic(III), leading to a dimin ished removal of endogenous DNA lesions and of DNA damage induced by enviro nmental agents, which in turn may increase the risk of tumor formation. Nev ertheless, the underlying mechanisms are quite different, depending for exa mple on the ability of toxic metal ions to compete with magnesium ions or t o displace zinc ions in zinc finger structures of DNA repair enzymes. (C) 1 998 Elsevier Science Ireland Ltd. All rights reserved.