Neonatal Diethylstilbestrol Prevents Spontaneously Developing Mammary Tumors

Summary

Our laboratory has been investigating the effects of perinatal exposure to hormonally active chemicals for predisposing adults to biochemical insult. In experiment I, female Sprague-Dawley rats were treated with diethylstilbestrol (DES) on days 2, 4, and 6 post-partum, followed by aflatoxin B₁ (AFB₁) during puberty and with phenobarbital (PB) in the drinking water from 6 through 16 months of age. Controls received propylene glycol (PG) or no treatment (NT) neonatally followed by similar AFB₁ and PB treatment. Incidences of gross mammary lesions were 67% and 8% in control and DES treated female rats, respectively. In experiment II female rats treated neonatally with PG or DES only have gross mammary lesion incidences of 79% and 13%, respectively, at 14 months of age. The results of experiment II suggest that the formation of tumors in experiment I is not due to the AFB₁ treatment, but is a consequence of spontaneous development. In experiment III, 6-month-old rats having received no PG treatment or DES neonatally followed by 50 mg dimethylbenzanthracene (DMBA) on day 50 had mammary tumor incidences of 100, 100, and 90%, respectively. The latency of tumor development was, however, greater in DES-treated females than in the NT and PG females. Our results reveal that neonatal exposure to the nonsteroidal estrogen, DES, exerts a chemopreventive effect on spontaneously developing but not on chemically induced mammary tumors. This may occur via altered imprinting mechanisms on the hypothalamic-pituitary axis or as a consequence of direct action on the differentiation of the mammary.