The biochemistry of preneoplasia in mouse skin.

After an introduction to the "Session on Skin" emphasizing that some early biochemical changes occurring in the two-stage model system for skin would be presented in the three following presentations, several background experiments were discussed. It was shown that a complete carcinogen for the skin (7,12-dimethylbenz[a]anthracene) provides both initiating and promoting components, but as the dose level of the carcinogen is lowered its promoting activity is lost while its initiating activity is retained. At the dose level that is completely carcinogenic, 7,12-dimethylbenz[a]anthracene exhibits the properties of a promoter; it stimulates RNA, protein, and DNA synthesis followed by cell division. At initiating doses, both the biochemical and morphological (increased mitosis) responses to treatment that are characteristic of promoters are lost; the remaining biochemical effects involve DNA and are attributed to initiating action. Some of the data supporting the concept that the mechanism of action of tumor promotion involves gene activation were reviewed.