Influence of Estradiol-17β, Progesterone and Hydrocortisone on 3-Methylcholanthrene-Induced Mammary Cancer in Intact and Ovariectomized Sprague-Dawley Rats

Abstract

Intact, ovariectomized and ovariectomized-adrenalectomized Sprague- Dawley rats, at the age of 50 days, were fed 10 mg of 3-methylcholanthrene (3-MC) by gastric tube 3 or 6 times each week for 7 weeks. Steroids were administered concurrently by the subcutaneous or intramuscular route. Mammary adenocarcinoma was observed in all intact rats. Mean tumor induction time was 52.7 ± 3.9 days for the group injected with sesame oil, 44.1 ± 1.5 for the group injected with progesterone (4 mg) and 47.5 ± 3.9 for the group injected with estradiol-17β (0.01 βg). In rats ovariectomized at 42 days of age, one week prior to treatment with 3-MC and steroids, breast cancer occurred in 63 % of the group injected with sesame oil, in 67 % of the group injected with progesterone, in 12% of the group injected with estradiol-17β and in 81 % of the groups injected with progesterone (4 mg) in combination with estradiol-17β (0.01 or 0.1 βg)- Mean tumor induction time was significantly prolonged in all ovariectomized groups. In rats ovariectomized at 30 days of age, 20 days prior to treatment with 3-MC and steroids, breast cancer occurred in 10 % of the group injected with sesame oil, in 44 % of the group injected with progesterone (2 mg) in combination with estradiol-17β (0.2 μg) and in 65% of the group injected with estradiol- 17β (0.2 μg) every 10th day and progesterone (2 mg) on intervening days. No breast tumors were observed in the group injected with estradiol-17β (0.2 μg). No correlation between the microscopic anatomy of breast tissue and the occurrence of cancer could be established. The intense lobule-alveolar development induced by progesterone alone was not observed in the mammary glands of rats given progesterone in combination with estrogen, or given estrogen alone. All adrenalectomized rats with ovaries intact had mammary cancer. Hydrocortisone reduced the number of tumors in intact rats and protected adrenalectomized rats against 3-MC toxicity, but had no influence on the incidence of breast cancer or mean tumor induction time. No mammary cancer was observed in adrenalectomized-ovariectomized rats. These observations support the concept that progesterone plays a critical role in mediating the carcinogenic response of breast tissue to 3-MC.