Azad Neelam, Rojanasakul Yon, Vallyathan Val
Department of Pharmaceutical and Pharmacological Sciences, West Virginia University, Morgantown, West Virginia, USA.
J Toxicol Environ Health B Crit Rev. 2008 Jan;11(1):1-15. doi: 10.1080/10937400701436460.
The lung is a highly specialized organ that facilitates uptake of oxygen and release of carbon dioxide. Due to its unique structure providing enormous surface area to outside ambient air, it is vulnerable to numerous pathogens, pollutants, oxidants, gases, and toxicants that are inhaled continuously from air, which makes the lung susceptible to varying degrees of oxidative injury. To combat these unrelenting physical, chemical, and biological insults, the respiratory epithelium is covered with a thin layer of lining fluid containing several antioxidants and surfactants. Inhaled toxic agents stimulate the generation of reactive oxygen/nitrogen species (ROS/RNS), which in turn provoke inflammatory responses resulting in the release of proinflammatory cytokines and chemokines. These subsequently stimulate the influx of polymorphonuclear leukocytes (PMNs) and monocytes into the lung so as to combat the invading pathogens or toxic agents. In addition to the beneficial effects, persistent inhalation of the invading pathogens or toxic agents may result in overwhelming production of ROS/RNS, producing chronic inflammation and lung injury. During inflammation, enhanced ROS/RNS production may induce recurring DNA damage, inhibition of apoptosis, and activation of proto-oncogenes by initiating signal transduction pathways. Therefore, it is conceivable that chronic inflammation-induced production of ROS/RNS in the lung may predispose individuals to lung cancer. This review describes the complex relationship between lung inflammation and carcinogenesis, and highlights the role of ROS/RNS in cancer development.
肺是一个高度特化的器官，它有助于氧气的摄取和二氧化碳的释放。由于其独特的结构为外界环境空气提供了巨大的表面积，它易受从空气中持续吸入的多种病原体、污染物、氧化剂、气体和毒物的影响，这使得肺易受到不同程度的氧化损伤。为了抵御这些持续不断的物理、化学和生物侵害，呼吸道上皮覆盖着一层含有多种抗氧化剂和表面活性剂的薄衬液。吸入的有毒物质会刺激活性氧/氮物种（ROS/RNS）的产生，进而引发炎症反应，导致促炎细胞因子和趋化因子的释放。这些物质随后会刺激多形核白细胞（PMN）和单核细胞流入肺部，以对抗入侵的病原体或有毒物质。除了有益作用外，持续吸入入侵的病原体或有毒物质可能会导致ROS/RNS的过度产生，从而引发慢性炎症和肺损伤。在炎症过程中，ROS/RNS产生的增加可能会通过启动信号转导通路诱导反复的DNA损伤、抑制细胞凋亡以及激活原癌基因。因此，可以想象，肺部慢性炎症诱导的ROS/RNS产生可能使个体易患肺癌。这篇综述描述了肺部炎症与致癌作用之间的复杂关系，并强调了ROS/RNS在癌症发展中的作用。
