The leukemogenic action of phorbol.

The unesterified, water-soluble compound phorbol, which does not act as a promoting agent for skin carcinogenesis when applied topically (although phorbol esters extracted from croton seed oil display pronounced activity), was tested in female SWR mice for promoting action by the systemic route, in the hope of overcoming a suspected solubility barrier in the skin. The results were negative. A high incidence of leukemias developed, however, both in the group receiving preliminary skin painting with 7,12dimethylbenz(a)anthracene followed by phorbol injections and in the phorbol control group. The tumors were of lymphoid origin, mostly nonthymic. There were also many reticulum cell sarcomas in the phorbol-treated mice, but the incidence did not appear to be higher than in the control groups. The potential value of phorbol as a chemical leukemogenic agent for the study of the mechanism of leukemogenesis is discussed.