Abstract
Inbred, female Sprague-Dawley rats were neonatally androgenized at the age of 2 days by subcutaneous injections of 1.25 mg testosterone propionate and divided into 4 groups. At the age of 50 days, rats of all groups were given 20 mg 7, 12-dimethylbenz[a]anthracene (DMBA). Four weeks after the administration of DMBA, the rats in Group I remained intact, those in Group II were subjected to ovariectomy, while the animals in Groups III and IV were given 1 mg 17β-estradiol (E2) at 2-day intervals for 3 weeks. Additionally, the rats in Group IV were given 1 mg E2 at 2-day intervals for 3 weeks by intramuscular injection, starting from the 105th day after the administration of DMBA.The ovaries of the neonatally androgenized rats contained numerous large vesicular follicles and no corpora lutea, and the mammary glands of the animals in Groups I, III and IV consisted mainly of dilated acini containing milky secretions. In rats in Group I, mammary carcinomas and mammary dysplasias were induced. Rat mammary dysplasias were grossly characterized by gross cysts and solid masses. Solid masses were heteromorphic lesions and commonly consisted of several nodules with various microscopic features. These masses were subclassified into the 2 types of histological features that were predominant among the nodules: acinar adenosis and fibrotic adenosis. The induction of mammary carcinomas and mammary dysplasias was strongly suppressed by ovariectomy (Group II) as the development of mammary carcinomas and mammary dysplasias induced in neonatally androgenized rats are dependent on estrogens. The induction of mammary carcinomas was suppressed by injections of high doses of E2 for 21 days (Once in Group III and twice in Group IV). Conversely, the induction of mammary dysplasias was promoted by one time (Group III) but was suppressed by two times (Group IV) of E2. The results indicate that carcinoma cells and dysplasia cells induced by DMBA in neonatally androgenized rats differ in response to high doses of E2.
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