Intracellular signal transduction of cells in response to carcinogenic metals.
Epidemiological and animal studies suggest that several metals and metal-containing compounds are potent mutagens and carcinogens. These metals include chromium, arsenic, vanadium, nickel, and others. During the last two decades, chemical and cellular studies have contributed enormously to our understanding of the mechanisms of metal-induced pathophysiological processes. Although each of these metals is unique in its mechanism of action, some common signaling molecules, such as reactive oxygen species (ROS), may be shared by many of the carcinogenic metals. New techniques are now available to reveal the mechanisms of carcinogenesis in precise molecular terms. In this review, we focused our attentions on carcinogenic metal-induced signal transduction pathways leading to the activation of NF-kappaB, cell apoptosis and cell cycle progression, three crucial steps or events involved in the transformation and carcinogenesis. This review summarizes current knowledge and our recent studies concerning intracellular signal transduction pathways initiated by carcinogenic metals and the cross-talk that occurs among these pathways in cells in response to metals.
Chen
Fei
F
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA. lfd3@cdc.gov
Shi
Xianglin
X
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens / Q000009:adverse effects / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008670:Metals / Q000009:adverse effects / Q000494:pharmacology*; D008954:Models, Biological; D016328:NF-kappa B / Q000502:physiology; D017382:Reactive Oxygen Species; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects
D002273:Carcinogens; D018797:Cell Cycle Proteins; D008670:Metals; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014157:Transcription Factors