Petronek Michael S, Spitz Douglas R, Buettner Garry R, Allen Bryan G
Free Radical and Radiation Biology Program, Department of Radiation Oncology, Free Radical Metabolism and Imaging Program, Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USA.
Cancers (Basel). 2019 Jul 30;11(8):1077. doi: 10.3390/cancers11081077.
Iron (Fe) is an essential element that plays a fundamental role in a wide range of cellular functions, including cellular proliferation, DNA synthesis, as well as DNA damage and repair. Because of these connections, iron has been strongly implicated in cancer development. Cancer cells frequently have changes in the expression of iron regulatory proteins. For example, cancer cells frequently upregulate transferrin (increasing uptake of iron) and down regulate ferroportin (decreasing efflux of intracellular iron). These changes increase the steady-state level of intracellular redox active iron, known as the labile iron pool (LIP). The LIP typically contains approximately 2% intracellular iron, which primarily exists as ferrous iron (Fe). The LIP can readily contribute to oxidative distress within the cell through Fe-dioxygen and Fenton chemistries, generating the highly reactive hydroxyl radical (HO). Due to the reactive nature of the LIP, it can contribute to increased DNA damage. Mitochondrial dysfunction in cancer cells results in increased steady-state levels of hydrogen peroxide and superoxide along with other downstream reactive oxygen species. The increased presence of HO and O can increase the LIP, contributing to increased mitochondrial uptake of iron as well as genetic instability. Thus, iron metabolism and labile iron pools may play a central role connecting the genetic mutational theories of cancer to the metabolic theories of cancer.
铁（Fe）是一种必需元素，在广泛的细胞功能中发挥着重要作用，包括细胞增殖、DNA合成以及DNA损伤和修复。由于这些联系，铁与癌症发展密切相关。癌细胞中铁调节蛋白的表达经常发生变化。例如，癌细胞经常上调转铁蛋白（增加铁的摄取）并下调铁转运蛋白（减少细胞内铁的外流）。这些变化增加了细胞内氧化还原活性铁的稳态水平，即所谓的不稳定铁池（LIP）。LIP通常包含约2%的细胞内铁，其主要以亚铁（Fe）形式存在。LIP可通过铁-双氧和芬顿化学反应轻易地导致细胞内的氧化应激，产生高反应性的羟基自由基（HO）。由于LIP的反应性，它会导致DNA损伤增加。癌细胞中的线粒体功能障碍会导致过氧化氢和超氧化物以及其他下游活性氧的稳态水平升高。HO和O的增加会增加LIP，导致线粒体对铁的摄取增加以及遗传不稳定性。因此，铁代谢和不稳定铁池可能在将癌症的遗传突变理论与癌症的代谢理论联系起来方面发挥核心作用。
