Promotion of mammary carcinogenesis and leukemogenic action by phorbol in virgin female Wistar rats.

Twice-weekly i.p. injections of 4 mg phorbol for 10 weeks, after a single feeding of 6mg 7,12-dimethylbenz(a)anthracene (DMBA), in virgin female Wistar rats led to a significant augmentation of mammary tumor induction (78%) as com pared to that resulting from 6 mg DMBA alone (21%). A slight effect, of doubtful significance, was observed when such phorbol treatment was given after feeding 2 mg DMBA and there was no effect after 0.25 mg DMBA. No mammary tumors developed in the rats receiving phorbol alone for 10 weeks, and 18% of the untreated controls (after a very long latent period) developed tumors. Continuation of the phorbol treatment in the phorbol control group for a total period of 9 months resulted in a very high incidence of lymphatic leukemia (94%, as compared to 2% in the untreated controls). However, the latent period was more than twice as long as in 2 other groups of rats that received a single dose of DMBA p.o., followed by only 10 weeks of phorbol injections. The thymus was involved in every case, in contrast to the previous findings in SWR mice similarly treated with phorbol, in which the induced leukemia was predominantly nonthymic. The results are discussed in relation to (a) the specific problem of promotion in mammary carcinogenesis, (b) the more general problem of systemic promoting action by phorbol, and (c) the possible meaning of the differences in pattern of leukemogenic response according to the species of animal used.