Pall M L
Proc Natl Acad Sci U S A. 1981 Apr;78(4):2465-8. doi: 10.1073/pnas.78.4.2465.
A two-stage model of carcinogenesis is proposed based on recent evidence for the occurrence of proto-oncogenes in the vertebrate genome, evidence for gene amplification during carcinogenesis, and studies of the action of tumor promoters. The model is baed on the view that an increase in the level of gene product from such proto-oncogenes is sufficient to induce neoplastic transformation. It proposes that the initial step in carcinogenesis (initiation) is a mutation producing a tandem duplication of a proto-oncogene. Gene amplification can then occur by successive unequal sister chromatid crossing-over events in several cell cycles until sufficient gene product is produced to transform the cell.
基于脊椎动物基因组中原癌基因存在的最新证据、致癌过程中基因扩增的证据以及肿瘤启动子作用的研究，提出了一个两阶段致癌模型。该模型基于这样一种观点，即来自此类原癌基因的基因产物水平的增加足以诱导肿瘤转化。它提出致癌作用的初始步骤（启动）是产生原癌基因串联重复的突变。然后，在几个细胞周期中通过连续的不等姐妹染色单体交叉事件可发生基因扩增，直到产生足够的基因产物来转化细胞。
