El Nachef Laura, Bouchet Audrey, Bourguignon Michel, Foray Nicolas
Inserm U1296 Unit, "Radiation: Defense, Health and Environment", 28 Rue Laennec, 69008 Lyon, France.
Département de Biophysique et Médecine Nucléaire, Université Paris Saclay, Versailles St. Quentin-en-Yvelines, 78035 Versailles, France.
Cancers (Basel). 2024 May 31;16(11):2104. doi: 10.3390/cancers16112104.
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.
虽然癌症是记录最为详尽的疾病之一，但正常细胞如何癌变仍存在争议。为解决这个问题，在本综述的第一部分，我们研究了自古至今一系列关于致癌作用的理论。体液学说由希波克拉底、亚里士多德和盖伦提出，将癌症解释为酸性过多的黑胆汁。1628年哈维发现血液循环，摧毁了体液学说的基础，但复兴了同样由亚里士多德提出的自然发生假说。1859年，巴斯德提出的微生物理论证明了最后这一理论的不相关性，并促成了胚芽癌理论的出现，该理论与癌症的细胞理论相对，后者分别认为癌症是由微生物或转化细胞引起的。由于诱变和细胞增殖方面的进展，这些理论通过启动、促进和进展的概念得到了逐步完善。在本综述的第二部分，讨论了致癌作用方面的最新发现和范式，特别是蛋白质ATM的作用，它是应激反应的主要参与者，参与诱变和细胞增殖，以便更好地了解致癌作用的当前技术水平。
