Nonneoplastic changes induced in female c3h mice by chronic exposure to diethylstilbestrol or 17β‐estradiol

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Abstract
The long-term nonneoplastic effects of estrogenic diets were studied in female C3H/HeJ and C3HeB/FeJ mice. C3H/HeJ mice received diets containing 0, 10, 100 or 500 ppb diethylstilbestrol (DES) or 100, 1000 or 5000 ppb 17.beta.-estradiol (E2) from 6 to 110 wk of age. C3HeB/FeJ females were fed diets containing nominal concentrations of 0, 10, 100 or 500 ppb DES from 6 to 136 wk of age. Responses of both strains to DES were qualitatively identical. Histological changes in the reproductive tract induced or increased by DES in both strains and by E2 in C3H/HeJ mice included stromal mucoid changes in the vagina and cervix, epithelial keratinization in the vagina, and glandular hyperplasia in the uterine horns. Increasing doses above 10 ppb DES or 100 ppb E2 increased the prevalence and, in some cases, severity of these responses. Dose-responses to DES for these endpoints were virtually indistinguishable in the 2 strains. At 10 ppb DES or 100 ppb E2 there were minimal or no observable effects. When the nonneoplastic dose-response data were compared with neoplastic dose-response data previously reported, no consistent relation between doses causing neoplastic and nonneoplastic responses was seen for the 2 estrogens.