Progress and prospects of reactive oxygen species in metal carcinogenesis.
Progress and prospects of reactive oxygen species in metal carcinogenesis.
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金属癌发生中活性氧的进展和前景。
DOI：
10.1007/s40495-016-0061-2
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发表时间：
2016-08
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环境金属暴露诱发的致癌作用是一个重大的公共健康问题。金属致癌的确切机制仍然难以捉摸。在过去的几十年中，金属诱导的活性氧（ROS）的产生与金属致癌机制之间的关系已经建立。致癌过程是一个非常复杂的过程。在金属致癌或细胞转化的早期阶段，高水平的ROS通过引起DNA损伤、遗传不稳定性、表观遗传改变和代谢重编程而致癌，导致恶性转化。在金属致癌作用的第二阶段或金属转化细胞的癌症发展中，低水平的ROS通过促进细胞凋亡抗性而致癌。金属转化的细胞具有自噬缺陷的性质，导致p62的积累和Nrf2的组成性激活，并导致更高水平的抗氧化剂、降低水平的ROS、抗凋亡、炎症和血管生成。本文综述了金属致癌作用的最新研究进展，重点介绍了金属致癌作用早期（细胞转化）和晚期（细胞转化后）细胞事件的差异。
Carcinogenesis induced by environmental metal exposure is a major public health concern. The exact mechanisms underlying metal carcinogenesis remain elusive. In the past few decades, the relationship between metal induced generation of reactive oxygen species (ROS) and the mechanism of metal carcinogenesis has been established. The carcinogenic process is a very complex one. In the early stage of metal carcinogenesis or cell transformation high levels of ROS are oncogenic by causing DNA damage, genetic instability, epigenetic alteration, and metabolic reprogramming, leading to malignant transformation. In the second stage of metal carcinogenesis or the cancer development of metal-transformed cells, low levels of ROS are carcinogenic by promoting apoptosis resistance. The metal-transformed cells have the property of autophagy deficiency, resulting in accumulation of p62 and constitutive activation of Nrf2, and leading to higher levels of antioxidants, decreased levels of ROS, apoptosis resistance, inflammation, and angiogenesis. This review summarizes the most recent development in the field of metal carcinogenesis with emphasis on the difference in cellular events between early (cell transformation) and late (after cell transformation) stages of metal carcinogenesis.