Chu E H, Trosko J E, Chang C C
J Toxicol Environ Health. 1977 Jul;2(6):1317-34. doi: 10.1080/15287397709529533.
A number of circumstantial lines of evidence are consistent with the somatic mutation theory of carcinogenesis, but there has been a paucity of experimental data that either support or contradict the genetic theory. In this paper, we summarize the predictions, the recent experimental approaches, and the problems involved in testing the theory. Results are presented that define the conditions and demonstrate the existence of two-stage processes of mutagenesis and carcinogenesis in vitro. We conclude that mutagenesis is responsible for the initiation of carcinogenesis and an epigenetic mechanism is responsible for its promotion. Carcinogenic agents can induce a stable transformation of a cell by either mutation or epigenetic alteration in gene expression. This conclusion has led us to propose a new integrative theory of carcinogenesis, encompassing the tenets of four main theories: (1) the mutation and epigenetic basis for carcinogenesis, (2) the two-stage theory of carcinogenesis, (3) a general theory of carcinogenesis, and (4) the somatic deletion mutation theory of carcinogenesis.
许多间接证据与癌症发生的体细胞突变理论相一致，但支持或反驳该遗传学理论的实验数据一直很匮乏。在本文中，我们总结了该理论的预测、近期的实验方法以及检验该理论所涉及的问题。展示了确定条件并证明体外诱变和致癌两阶段过程存在的结果。我们得出结论，诱变作用是致癌作用起始的原因，而一种表观遗传机制则是致癌作用促进的原因。致癌剂可通过基因表达中的突变或表观遗传改变诱导细胞发生稳定转化。这一结论促使我们提出一种新的综合癌症发生理论，该理论包含四个主要理论的原则：（1）癌症发生的突变和表观遗传基础，（2）癌症发生的两阶段理论，（3）癌症发生的一般理论，以及（4）癌症发生的体细胞缺失突变理论。
