title: Metal interaction with redox regulation: an integrating concept in metal carcinogenesis?
abstract: The carcinogenicity of cadmium, arsenic, and chromium(VI) compounds has been recognized for some decades. However, the underlying molecular mechanisms seem to be complex and are not completely understood at present. Although, with the exception of chromium(VI), direct DNA damage seems to be of minor importance, interactions with DNA repair processes, tumor suppressor functions, and signal transduction pathways have been described in diverse biological systems. In addition to the induction of damage to cellular macromolecules by reactive oxygen species, the interference with cellular redox regulation by reaction with redox-sensitive protein domains or amino acids may provide one plausible mechanism involved in metal carcinogenicity. Consequences are the distortion of zinc-binding structures and the activation or inactivation of redox-regulated signal transduction pathways, provoking metal-induced genomic instability. Nevertheless, the relevance of the respective mechanisms depends on the actual metal or metal species under consideration and more research is needed to further strengthen this hypothesis.
authors.affiliation: Institute of Applied Biosciences, Department of Food Chemistry and Toxicology, Karlsruhe Institute of Technology, 76131 Karlsruhe, Germany. Andrea.Hartwig@kit.edu
authors.forename: Andrea
authors.initials: A
authors.lastname: Hartwig
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D008670:Metals / Q000633:toxicity*; D008954:Models, Biological; D009369:Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D008670:Metals; D017382:Reactive Oxygen Species