Speciation 98: Abstracts

Nickel is now recognised to be an essential element for bacteria, plants, animals and humans.¹ However, it is nickel toxicological rather than beneficial effects that are in the focus of research. The most studied aspects of the nickel toxicity are those concerning the molecular mechanisms of metal carcinogenicity.² The most likely mechanism for nickel carcinogenic action is that based on oxidative reactions. The direct metal - biomolecule co-ordination seems to be a less important factor in the metal toxicity. It is evident that both the metal ion co-ordination to biomolecules and the oxidative reactions induced by metals critically depend on the metal ion species involved, its physicochemical properties and reactivity.³

No dedicated nickel binding proteins are currently known. The intracellular speciation of Ni(II), crucial for nickel carcinogenesis, is not understood well, except for the fact that nickel concentrates predominantly in the cell nucleus.⁴ Histones are major nuclear proteins, at a formal concentration of 3 mM. We have identified two potential Ni(II) binding sites in the histone octamer: -CAIH- (H3 110-113), and -ESHH- (H2A 121-124).⁵ Our further studies⁶ indicate that at low nickel exposure the order of intracellular binding should be His > -ESHH- > -CAIH- and at high nickel it changes into -ESHH- > -CAIH- > His. Such variations of speciation have a distinct impact on molecular mechanisms of carcinogenesis, while His and -CAIH- complexes are strong oxidation activators and -ESHH- ones are not, but may mediate damage to genetic material through non-oxidative reactions. ⁶

References

1. M. A. Halcrow, and G. Christou, Chem. Rev., 94, 2421 (1994).
2. K. S. Kasprzak, Environm. Carcinogenesis, 13, 411 (1995).
3. H. Kozlowski, in Cytotoxic, Mutagenic and Carcinogenic Potential of Heavy Metals Related to Human Environment, N.Hadjiliadis, ed., Kluwer, London 1997, pp. 549-558.
4. S. R. Patierno, M. Sugiyama, and M. Costa, J. Biochem. Toxicol. 2, 13 (1987).
5. W. Bal and K. S. Kasprzak, in Cytotoxic, Mutagenic and Carcinogenic Potential of heavy Metals Related to Human Environment, N.Hadjiliadis, ed., Kluwer, London 1997, pp. 107-121.
6. W. Bal, K. Bialkowski, J. Lukszo and K. S. Kasprzak, submitted

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