Interactions by Carcinogenic Metal Compounds with DNA Repair Processes

Some metal compounds, including arsenic, beryllium, cadmium, chromium and nickel have long been recognized as human and animal carcinogens, while for other as antimony, cobalt, lead and vanadium their carcinogenic action are probable or possible. Except chromium (VI), carcinogenic metals are only weak mutagens in mammalian cells and often inactive in bacterial assays. Since the mutagenicity in bacterial assays indicates reactivity with DNA, metals are thought to exert genotoxicity mainly by indirect mechanisms. The four main, partly overlapping, DNA repair pathways operating in mammalian cells are base excision, mismatch, nucleotide excision and recombinational repair; each of repair pathways is involved in the removal of the specific DNA lesions. In addition, many carcinogenic metal compounds at low concentrations have been identified as inhibitors of the repair of DNA damage caused by other xenobiotics or endogenous factor. Furthermore, DNA is not only damaged by environmental mutagens including UV-light and polycyclic aromatic hydrocarbons, but also by reactive oxygen species generated from the same metallic elements. Failure to repair DNA damage can result in the accumulation of damaged DNA, mutation and carcinogenesis.