EFFECT OF ESTRONE ON THE GROWTH OF 7,12-DIMETHYLBENZ(A)ANTHRACENE-INDUCED MAMMARY-CARCINOMA IN THE RAT - A MODEL OF POSTMENOPAUSAL BREAST-CANCER

Estradiol (E(2)) is well known as stimulator of the growth of 7,12-dim ethylbenz(a)anthracene (DMBA)-induced mammary tumors. The effect of es trone (E(1)), however, has not been described in this model of human b reast cancer. As E(1) is the predominant estrogen precursor in postmen opausal women, we have investigated the effect of this steroid and, si multaneously, the potential role of the enzyme required for interconve rsion of the weak estrogen E(1) into the potent estrogen E(2), namely 17 beta-hydroxysteroid dehydrogenase, in the growth of DMBA-induced ma mmary carcinoma in the rat. Treatment for 20 days of ovariectomized an imals bearing DMBA-induced mammary tumors with twice daily doses of 0. 375, 0.75, 1.5, and 3.0 mu g E(1) increased total tumor area by 48%, 1 01%, 116%, and 129%, respectively. Treatment with the highest dose of E(1) increased progesterone receptor levels by 20.4- and 2.3-fold in t he DMBA-induced tumors and uterus, respectively. After treatment with E(1), the concentration of this steroid was similar in the serum and t umor tissue, whereas concentrations of E(2) were approximately 3-fold higher in the tumor tissue compared to serum. Treatment with a 1.0-mu g dose of E(1) caused a 60% increase in tumoral 17 beta-hydroxysteroid dehydrogenase activity in ovariectomized animals, thus favoring E(2) formation from E(1) in tumors. In addition, treatment with the 1.0-mu g dose of E(1) or 0.1 mu g E(2) gave similar stimulatory effects on tu mor growth and uterine weight in ovariectomized animals; the values we re comparable to those found in intact animals. The present data indic ate that ovariectomized rats bearing DMBA-induced mammary tumors and t reated with E(1) can be a useful model of postmenopausal breast cancer .