Reddy A L, Fialkow P J
Nature. 1983;304(5921):69-71. doi: 10.1038/304069a0.
The discovery of a two-stage mechanism of carcinogenesis in mouse skin, with initiation and promotion as independent components, provided new approaches to the study of the development of neoplasms in experimental animals and humans. However, it is not clear how the carcinogen and promoting agent are involved at different steps in the development of papillomas and carcinomas. Here we have used cell markers in mice to study the mechanism of development of papillomas induced by the classical method of two-stage skin tumorigenesis (initiation with subtumorigenic doses of a carcinogen followed by promotion with phorbol esters) and by multiple treatments with initiating doses of a carcinogen. Our results show that papillomas induced by repeated carcinogen applications arise from significantly more cells than those induced by the carcinogen-promoter regimen.
在小鼠皮肤中发现了致癌作用的两阶段机制，起始和促进作为独立的组成部分，为研究实验动物和人类肿瘤发生发展提供了新方法。然而，尚不清楚致癌物和促癌剂在乳头状瘤和癌的发展过程中是如何在不同步骤发挥作用的。在此，我们利用小鼠体内的细胞标记物，研究经典的两阶段皮肤肿瘤发生方法（用亚致癌剂量的致癌物启动，随后用佛波酯促进）以及多次给予启动剂量致癌物所诱导的乳头状瘤的发生机制。我们的结果表明，重复应用致癌物诱导的乳头状瘤起源的细胞数量比致癌物-促癌剂方案诱导的乳头状瘤多得多。
