The co-action of estrogen in the induction of tumors of the mouse uterus treated with 20-methylcholanthrene [abstract].

Abstract

Over 200 young mature and mature CF1 mice were ovariectomized and their uterine horns implanted bilaterally with circa 2 mg methylcholanthrene (MCA) by trocar. Subcutaneous injections of 20 mcg diethylstilbestrol in 0.05 ml oil were then made 3x weekly in equivalent groups for 0, 4, 6, 10, 12, 14, 16, 18, and 20 weeks. All animals died or were sacrificed by 180 days following MCA implantation. Nearly 1/2 of the 57 mice surviving estrogen treatment and living at least 100 days after MCA implantation developed uterine tumors. Most of the affected mice developed tumors in both cornua. Tumors in mice receiving estrogen for the longer periods were especially large and aggressive. Histologically, they were predominantly sarcomatous, but adenocarcinomas were induced in the approximate ratio of 1:4. The incidence of tumors in mice treated with estrogens for 12-20 weeks was significantly higher than in those given extrogen 4-10 weeks. Only 1 prominent uterine tumor was found in 8 mice which survived 102-168 days after bilateral MCA implantation and 12 subcutaneous injections of 60 mcg diethylstilbestrol in 4 weeks. Diethylstilbestrol, when administered for a sufficient period, seemingly acts as a cocarcinogen in mice, accelerating the induction of uterine tumors by MCA and perhaps stimulating their growth.