CHEMOPREVENTION BY DIETARY DEHYDROEPIANDROSTERONE AGAINST PROMOTION PROGRESSION PHASE OF RADIATION-INDUCED MAMMARY TUMORIGENESIS IN RATS/

When pregnant rats received whole body irradiation with 260 cGy gamma- ray at day 20 of pregnancy, and were then implanted with a diethylstil bestrol (DES) pellet for an experimental period of 1 year under feedin g of a control diet, a high incidence (96.2%) of mammary tumors was ob served. Administration of dietary 0.6% dehydroepiandrosterone (DHEA) t ogether with DES implantation significantly decreased the incidence (3 5.0%) of mammary tumors. The first appearance of palpable tumors in th e DHEA-fed group was 4.5 months later than that in the control group. For clarification of the mechanism of the chemopreventive action, we m easured hormone levels in the serum of DHEA-fed rats. In the DHEA diet rats, the concentration of estradiol-17 beta exceeded, by approximate ly 6-fold, that in the control rats, while the levels of progesterone and prolactin were decreased by 30 and 45%, respectively. Interestingl y, DHEA feeding prevented DES-induced hypertrophy of pituitary glands and DES-induced high level of prolactin in pituitary glands detected b y immunohistochemical studies, but stimulated the development of mamma ry glands more than that in control rats treated with DES alone. These findings suggest that DHEA has a potent preventive activity against t he promotion/progression phase of radiation-induced mammary tumorigene sis. The mechanism of chemoprevention by change of endocrinological en vironment is discussed.