文章：

当DNA突变与细胞增殖相互作用：致癌理论的历史叙事

When DNA Mutations Interplay with Cellular Proliferation: A Narrative History of Theories of Carcinogenesis

原文发布日期：31 May 2024

DOI: 10.3390/cancers16112104

类型: Article

开放获取: 是

英文摘要：

While cancer is one of the most documented diseases, how normal cells become cancerous is still debated. To address this question, in the first part of this review, we investigated the long succession of theories of carcinogenesis since antiquity. Initiated by Hippocrates, Aristotle, and Galen, the humoral theory interpreted cancer as an excess of acid, the black bile. The discovery of the circulation of blood by Harvey in 1628 destroyed the basis of the humoral theory but revived the spontaneous generation hypothesis which was also promoted by Aristotle. In 1859, the theory of microbes promoted by Pasteur demonstrated the irrelevance of this last theory and contributed to the emergence of the germ cancer theory, opposed to the cellular theory of cancer, in which cancer was supposed to be caused by microbes or transformed cells, respectively. These theories were progressively refined by the notions of initiation, promotion, and progression thanks to advances in mutagenesis and cellular proliferation. In the second part of this review, recent discoveries and paradigms in carcinogenesis, notably the role of the protein ATM, a major actor of the stress response involved in both mutagenesis and cellular proliferation, were discussed to better understand the current state of the art of carcinogenesis.

摘要翻译： 

尽管癌症是研究记录最为详尽的疾病之一，正常细胞如何癌变仍是学界争论的焦点。为探讨这一问题，本文综述的第一部分系统梳理了自古希腊时期以来关于致癌机制的漫长理论演变。由希波克拉底、亚里士多德和盖伦创立的体液学说将癌症解释为酸性黑胆汁的过度积聚。1628年哈维发现血液循环后，体液学说的理论基础被瓦解，但亚里士多德曾倡导的自然发生说得以复兴。1859年巴斯德提出的微生物理论不仅否定了自然发生说，更催生了两种对立观点：主张微生物致病的癌症细菌学说与支持细胞癌变的细胞起源学说。随着诱变机制与细胞增殖研究的突破，关于癌变的启动、促进和演进三阶段理论逐步完善。在综述第二部分，通过探讨致癌机制的最新发现与范式（特别是应激反应关键蛋白ATM在诱变与细胞增殖中的双重作用），系统阐释了当代致癌机制研究的前沿进展。

原文链接：

When DNA Mutations Interplay with Cellular Proliferation: A Narrative History of Theories of Carcinogenesis