Potter V R
Yale J Biol Med. 1980 Sep-Oct;53(5):367-84.
Three major theories of cancer--somatic mutation, virus causation, and faulty differentiation--are proposed to involve alterations in DNA structure. Each results finally in terms of failures in the normal intercellular communication that involves feedback between differentiated cells acting on less differentiated cells still capable of proliferation. The historical background of the latter idea is traced to Osgood, Weiss and Kavanau, and to Iversen. The historical background of concepts of initiation and promotion are traced to Berenblum and Mottram and the Boutwell concept of promotion as gene activation is cited. It is proposed that gene activation by promoters is a valid concept and that it results from the blocking of the normal intercellular communication postulated by Osgood and others. The problem of explaining the low probability of cancer following initiators or promoters acting alone is cited as a problem in basic science. A hypothesis to solve the problem is proposed: Cancer results from two of more relevant mutations: promoters enhance proliferation of cells with one relevant mutation, thereby increasing the probability of obtaining a cell with two relevant mutations. A new scheme of five stages of hepatocarcinogenesis is proposed in terms of the hypothesis and available data.
癌症的三种主要理论——体细胞突变、病毒致癌和分化异常——被认为涉及DNA结构的改变。每一种理论最终都导致正常细胞间通讯的失败，这种通讯涉及分化细胞对仍能增殖的低分化细胞的反馈作用。后一种观点的历史背景可追溯到奥斯古德、韦斯和卡瓦瑙以及艾弗森。引发和促进概念的历史背景可追溯到贝伦布卢姆和莫特拉姆，并引用了博特韦尔关于促进作为基因激活的概念。有人提出，启动子引起的基因激活是一个有效的概念，它是由奥斯古德等人假定的正常细胞间通讯的阻断所导致的。解释单独使用引发剂或启动子后癌症发生概率较低的问题被视为基础科学中的一个问题。提出了一个解决该问题的假说：癌症是由两个或更多相关突变导致的；启动子增强具有一个相关突变的细胞的增殖，从而增加获得具有两个相关突变的细胞的概率。根据这一假说和现有数据，提出了肝癌发生的五个阶段的新方案。
