Papillomas induced by initiation-promotion differ from those induced by carcinogen alone.

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.