The role of oxidative stress in mechanisms of metal-induced carcinogenesis.
Metals are necessary for the normal functioning of cells and the survival of organisms. However, exposure to higher than the physiological levels of several metals may lead to tumor development. Although the exact molecular mechanism(s) of metal-induced carcinogenesis is not clear, a vast body of evidence indicates that metal-induced generation of reactive oxygen species (ROS) may play a central role in this process. Two main pathways of ROS-induced effects are discussed in this chapter: (i) increased DNA damage induced either directly or indirectly by impeding DNA repair, and (ii) modulation of nuclear transcriptional factor activities, such as NF-kappaB and AP-1, through mitogen-activated protein kinases signal transduction mechanisms.