Effect of Hormone Stimulation, Dose, and Time of Administration of Carcinogen on Carcinogen-Induced Mammary Tumors From Preneoplastic Nodule Outgrowths

Summary

The tumorigenic effect of two chemical carcinogens, 7,12-dimethylbenz[a]anthracene (DMBA) and urethan, and of γ-irradiation were analyzed further on the nodule outgrowth line D1. Nodule outgrowth line D1 treated with DMBA and urethan produced 68 and 83% tumors, respectively, whereas irradiated outgrowths produced only 23%. Prolonged hormone stimulation by a single pituitary isograft enhanced the tumorigenic effect of DMBA, had no effect on urethan-induced tumorigenesis, and inhibited irradiation-induced tumorigenesis. Nodule outgrowths were exposed to various doses of DMBA and urethan. Outgrowths exposed to 1.0 mg and 1.5 mg DMBA produced the same tumor incidence (68%), whereas outgrowths exposed to 0.5 mg produced only 50% tumors. The various doses of urethan produced mammary tumors in the following order: 200 mg >100 mg = 80 mg >60 mg = 40 mg >20 mg. The time of administration of urethan was important in determination of the ultimate tumor incidence and the rate of tumor formation. Outgrowths exposed to urethan between 3 and 5 weeks after transplantation produced tumors earlier and at a higher incidence than outgrowths exposed to urethan at later periods. The implications of these results are discussed as to similar findings of D1 nodule outgrowths treated with 3-methycholanthrene.