Chen Fei, Shi Xianglin
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA.
Crit Rev Oncol Hematol. 2002 Apr;42(1):105-21. doi: 10.1016/s1040-8428(01)00211-6.
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.
流行病学和动物研究表明，几种金属及含金属化合物是强效诱变剂和致癌物。这些金属包括铬、砷、钒、镍等。在过去二十年中，化学和细胞研究极大地增进了我们对金属诱导的病理生理过程机制的理解。尽管这些金属中的每一种在其作用机制上都是独特的，但一些常见的信号分子，如活性氧（ROS），可能为许多致癌金属所共有。现在有了新技术，可以从精确的分子层面揭示致癌机制。在本综述中，我们将注意力集中在致癌金属诱导的信号转导途径上，这些途径导致核因子κB激活、细胞凋亡和细胞周期进程，这是转化和致癌过程中涉及的三个关键步骤或事件。本综述总结了关于致癌金属引发的细胞内信号转导途径以及细胞中这些途径之间因金属而发生的相互作用的当前知识和我们最近的研究。
