Inhibition of Mammary Tumors by Pretreatment with 17β‐Estradiol in F344 Rats Induced with N‐Methyl‐N‐nitrosourea

The influence of 17β‐estradiol (E2) and prolactin was studied on N‐methyl‐N‐nitrosourea (MNU)‐induced mammary carcinomas (MCAs) in rats. MNU was intravenously injected once into seven‐week‐old female F344 rats at a dose of 50 mg/kg body weight. Groups of rats also received either 2.5 mg of E2 or a continuous supply of prolactin and/or growth hormone via transplanted MtT/F84 (mammo‐somatotropic pituitary tumor). Rats were observed for up to 36 weeks after MNU administration. Although simultaneous administration of MNU and E2 did not much affect the occurrence of MCAs as compared to administration of MNU alone, rats treated with 2.5 mg of E2 for two weeks before MNU administration had significantly reduced occurrence of MCAs compared to those given MNU alone. In contrast, rats with MNU plus MtT/F84 showed high incidence and shortened latency of MCAs and they also had a high incidence of clitorial gland hyperplasias. Average pituitary weights and serum prolactin levels in E2‐treated rats were greatly increased compared to those of MNU‐alone rats. Average serum E2 levels were about 100 ng/ml in E2‐treated rats and 0.05 ng/ml in rats without E2 treatment. Serum prolactin levels were greatly increased in rats with MtT/F84. The results indicated that pretreatment with E2 before MNU administration was inhibitory while increased prolactin caused by grafting MtT/F84 after MNU injection was promotive for the occurrence of MCAs in female F344 rats.