Pure and Applied Chemistry

Abstract: The molecular mechanisms of carcinogenesis involving heavy metal ions are not yet fully understood. Histones surrounding DNA are believed to be primary targets for metal ion binding, and such interactions may play a direct or indirect role in metal-induced toxicity carcinogenesis. This paper reviews our results of approximately the last 10 years in this area, starting from small peptide fragments and models of various histones and ending with longer ones. It was found that almost all peptide models reacted strongly with metal ions, and in some cases the peptides in the presense of Cu(II) or Ni(II) were hydrolyzed. Oxidation of deoxyguanosine to 8-oxo-deoxyguanosine under physiological pH values was also observed in the presense of mild oxidation agents like H₂O₂ and certain metal ion–peptide complexes. With longer peptide chain models, a DNA strand breakage analysis was also carried out, indicating an increased DNA damage by Cu²⁺/H₂O₂ and Ni²⁺/H₂O₂ reaction mixtures. The results lead to proposals of possible mechanistic pathways of carcinogenesis caused by Cu(II) and Ni(II).