Growth Inhibition of a High Dose of 17 β-Estradiol and Ovariectomy on 7, 12-Dimethylbenz(a)anthracene-induced Mammary Carcinomas in Female Rats

In this study the inhibitory effect of a high dose of estrogen on mammary carcinoma growth was investigated, especially in relation to apoptosis and mitosis, and compared this to the effects of ovariectomy. A transplantable mammary carcinoma with estrogen receptors was induced in a female Sprague-Dawley rat by multiple intragastric intubations of 7, 12-dimethylbenz(a)anthracene. The mammary carcinoma was then transplanted into female rats, and on the 21st day after the transplantation the rats were divided into three groups. Rats in two of these groups were injected with either vehicle or 1.0 mg of 17β-estradiol three times a week, and rats in the remaining group were ovariectomized. Rats were sacrificed on either the 1st, 7th, 14th, or 21st day after the initial administration or ovariectomy. The growth of transplanted mammary carcinomas was suppressed in ovariectomized rats and rats treated with a high dose of 17β-estradiol. In the 17β-estradiol treated rats, the incidences of apoptotic cells and Apop Tag positive cells were higher than those of the intact control on the 7th to 21st day after the initial administration, and the incidences of mitotic cells and 5-Bromodeoxyuridine staining positive cells were higher only on the 7th day after the initial administration. Conversely, there was no difference between incidences of apoptotic cells and Apop Tag positive cells between the ovariectomized rats and the intact control throughout the treatment period, and incidences of mitotic cells and 5-Bromodeoxyuridine staining positive cells were lower in the ovariectomized rats on the 7th to 21st day after the ovariectomy. These results indicate that the growth inhibition of the mammary carcinoma in rats treated with a high dose of 17β-estradiol was related to apoptosis. In contrast, a decrease of cell proliferation is considered to be the mechanism responsible for the inhibitory effect of ovariectomy on the growth of the mammary carcinoma.