Effects of Short-term Pregnancy Hormone Treatment against N-Methyl-N-nitrosourea-induced Mammary Carcinomas in Female Lewis Rats

Aim: To study the effects of short-term pregnancy hormone treatment, estradiol and progesterone or prolactin, against pre-existing mammary cancer as well as newly developing mammary cancer by using the N-methyl-N-nitrosourea (MNU)-induced rat mammary cancer model. Materials and Methods: Three-week-old female Lewis rats (n=103) received an intraperitoneal injection of 50 mg/kg MNU. Nine weeks after the MNU injection, the rats received 3 weeks of hormone treatments, consisting of a subcutaneously implanted 0.5 mg estradiol-and 32.5 mg progesterone-containing pellet (EIP group, n=35) or four subcutaneous injections per week of 5 mg/kg perphenazine (PPZ group, n=38), a prolactin-releasing agent. The remaining rats did not receive hormones (control group, n=30). At 12 weeks of age (when the hormone treatments were started), 6 rats in each of the three groups had palpable tumors. These rats were sacrificed at 15 weeks of age, and the remaining rats were sacrificed at 19 weeks of age. The entire mammary glands and the palpable mammary tumors were histologically examined, and the development and growth of mammary tumors was compared. Results: Newly developing mammary tumors were suppressed and pre-existing ones regressed in the EIP group, while the development and growth of both newly developing cancers and pre-existing tumors were accelerated in the PPZ group as compared with the control group. Conclusion: Shortterm, pregnancy levels of estradiol and progesterone (but not prolactin) may be the most effective treatment against MNU-induced mammary tumors in female Lewis rats.