Effects of a norethynodrel-mestranol combination (enovid) on development and growth of carcinogen-induced mammary tumors in female rats.

Abstract

Female Sprague-Dawley rats that were housed in a temperature of approximately 75 degrees F and exposed to light 14 hours/day were studied to determine the effects of Enovid (E) on development and growth of 712-dimethylbenzanthracene (DMBA)-induced mammary tumors (MTs). Before MT development 87 immature female rats were divided into 3 groups and treated as follows: Groups 2 and 3 received a daily dose of 10 or 100 mcg E respectively beginning on Day 30 to Day 70. Controls (Group 1) received the same volume of corn oil. On Day 55 all animals were injected with 5 mg DMBA. After MT development 96 female rats 55 days of age were given a single iv injection of a lipid emulsion containing 5 mg DMBA. 65 days after carcinogen treatment the number and size of palpable mammary tumors were recorded. 1/2 of the rats were then divided into 3 groups: intact controls intact and given 10 mcg E and intact and given 100 mcg E. The remaining 1/2 were left untreated for 30 additional days examined at 150 days of age for tumors and divided into 3 equal groups; ovariectomized controls ovariectomized and given 10 mcg E and ovariectomized and given 100 mcg E. E was injected once daily for 25 consecutive days beginning at age 120 days (intact) or 150 days (ovariectomized). The injection of E into immature intact rats for 25 days before and 15 days after DMBA treatment resulted in a reduction of MTs per rat. Injection of 10 mcg of E for 25 days into mature intact rats bearing DMBA-induced MTs resulted in a moderate but significant increase in the number of MTs per rat. 100 mcg injections showed a significant decrease in number of MTs per rat as compared with the intact controls. Injection of 10 or 100 mcg of E for 25 days into mature ovariectomized rats bearing DMBA-induced tumors resulted in an increase in tumors compared with the ovariectomized controls. These results are believed to be due to the predominantly estrogenic action of E creating an increased prolactin secretion and stimulation of mammary growth. These data suggest that mammary growth-promoting agents such as E may be protective against the development of MTs by carcinogenic agents but may enhance growth of MTs already present.(AUTHORS MODIFIED)