Genotoxicity of metal ions: chemical insights

Abstract

The purpose of this review is to provide a reader with a brief account of current results and views in the area of genotoxicity of metal ions, with a special attention to underlying chemical mechanisms. The text is divided into six sections. Following a general introduction in Section 1, Section 2 describes main molecular mechanisms of formation of genotoxic lesions: hydrolysis, alkylation, and radical reactions of nucleobases and the phosphosugar DNA backbone. The basics of cellular repair of DNA lesions are also shortly presented. This section serves as a background source for Sections 3, 4, and 5. Section 3 covers the main mechanisms of metal ion genotoxicity, followed by Section 4, which describes genotoxicity of individual metals; i.e., of the confirmed carcinogens As, Be, Cd, Cr, and Ni, as well as of the suspected carcinogens Co, Cu, Fe, Pb, Pt, and 238U (also known as depleted uranium). The genotoxicity of exposures to metal mixtures is also discussed. Section 5 provides a critical overview of methodologies used for studying mutagenicity and carcinogenicity of metals; the final Section 6 summarizes the current state and future perspectives of research in genotoxic mechanisms of metal ions.