Molecular mechanisms in nickel carcinogenesis: modeling Ni(II) binding site in histone H4. Environ Health Perspect. 2002;110 Suppl 5:719-23. Rev

The carcinogenicity of nickel compounds has been confirmed and corroborated by numerous epidemiological studies in humans and carcinogenesis bioassays in animals [1]. Although the mechanisms of nickel-induced carcinogenesis are not well-known, they are believed to involve genetic and epigenetic routes. Nickel compounds influence carcinogenesis by interfering with a variety of cellular targets. We found that nickel is a potent inhibitor in vivo of histone H4 acetylation, in both yeast and mammalian cells [2]. It has preference to specific lysine residues in the N-terminal-S1GRGK5GGK8GLGK12GGAK16RH18RKVL22 histone H4, in which the sites of acetylation are clustered. The metal ion is able to bind histidine H18 in the N-terminal which protrude out from the nucleosome [3]. We also found that an excellent tumour marker recently discovered and specifically induced by nickel, Cap43 protein, has a new mono-histidinic motif consisting of ten amino acids TRSRSHTSEG repeated three times in the C-terminu