Interactions by carcinogenic metal compounds with DNA repair processes: toxicological implications

Even though compounds of nickel, arsenic, cobalt and cadmium are carcinogenic, their mutagenic potentials are rather weak. In contrast, they exert pronounced comutagenic effects, which may be explained by disturbances of different DNA repair systems. Thus, cobalt, arsenic, nickel and cadmium interfere with base and nucleotide excision repair, even though they affect different steps of the respective repair systems and act by different, not yet completely understood mechanisms. Potential target molecules for some metal ions are so-called zinc finger structures in DNA repair proteins, but each zinc finger protein exerts its own sensitivity towards toxic metal ions. Possible consequences of repair inhibitions are discussed in more detail for soluble and particulate nickel compounds, which have recently been shown to interfere with the repair of stable DNA adducts induced by benzo[a]pyrene (B[a]P). Since nickel compounds and polycyclic aromatic hydrocarbons such as B[a]P are frequently associated in the ambient air, in cigarette smoke and at many workplaces, an impaired removal of B[a]P-derived DNA adducts will lead to persistent DNA damage and thus increase the risk of mutations and tumor formation.