Tumor-promoting activity of phorbol and four diesters of phorbol in mouse skin.

Phorbol, the terpene alcohol found in the skin tumor-promoting components of croton oil, was isolated, and four diesters were synthesized from it. The tumor-promoting potencies of these compounds were tested in Charles River GDI mice and skin tumor-susceptible mice. The esters of high tumor-promoting ability (12-O-tetradecanoyl-phorbol-13acetate and phorbol-12,13-didecanoate) were effective in both lines of mice, but the compounds which were only weakly active or inactive in Charles River mice (phorbol-12,13-dibenzoate and phorbol) and a compound which was not tested in CD1 mice (phorbol-12,13-diacetate) have the ability to promote in the skin tumor-susceptible mice. The presence of a long-chain acid esterified to phorbol appears to be of greater importance in ordinary mice than in susceptible mice, in which phorbol alone possesses weak promoting activity.