Effects of perinatal exposure to a synthetic estrogen and progestin on mammary tumorigenesis in mice.

Abstract

The effects of perinatal exposure to synthetic estrogens and progestins on mammary tumorigenesis were studied in female C3H/HeN/MTV + mice. Mice were treated neonatally with 0.001 microgram/day diethylstilbestrol (DES), with 15 micrograms/day 17 alpha-hydroxyprogesterone caproate (HPC), or with oil on days 1-5 of life (birth = day 1). As adults, neonatally hormone-treated mice received long-term treatment with a synthetic estrogen and progestin combination or vehicle. Animals were palpated weekly for mammary gland tumors. The effect of treatment on the probability of tumor development was examined. Neonatal treatment with a low dose of DES increased the probability of mammary-gland tumor formation, whereas neonatal treatment with HPC had a slightly protective effect on tumorigenesis. Subsequent treatment of adult mice with synthetic steroids did not affect mammary gland tumorigenesis in neonatally DES-treated or oil-treated animals. There was a significant interaction between the effect of neonatal HPC treatment and subsequent steroid treatment on mammary tumorigenesis but examination of the data indicated that this interaction was due to the protective effect of HPC in the absence of subsequent exposure to synthetic steroids and the probability of tumor appearance in mice treated with both HPC and synthetic steroids as adults did not differ from that of neonatally oil-treated controls.