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Pure Appl. Chem., 2011, Vol. 83, No. 9, pp. 1751-1762

Published online 2011-06-24

Peptide models in the study of the mechanism of carcinogenesis by heavy metals

Gerasimos Malandrinos, Ana-Monica Nunes, Kimon Zavitsanos and Nick Hadjiliadis

Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece

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).