Effects of Fetal Exposure to Diethylstilbestrol on Mammary Tumorigenesis in Rats

Abstract

The aim of this study was to investigate the effect of fetal exposure to diethylstilbestrol (DES) on the induction of mammary tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female rats. Pregnant rats were fed only normal diet, diet mixed with 0.1 ppm DES throughout pregnancy period or diet mixed with 0.1, 1 or 10 ppm DES from day 13 of pregnancy till the end of pregnancy. Delivered pups were given 10 mg DMBA by gastric intubation at 50 days after birth and observed till 336 days after birth. Some rats exposed to DES throughout pregnancy and those from day 13 till the end of pregnancy showed endocrine disrupting effects such as absence of CL and active lactation in mammary glands at necropsy, while no abnormal estrus cycle such as persistent estrus was seen during the observation period until 88 days after birth. Fetal exposure to 0.1 ppm DES throughout pregnancy period, 0.1 and 1 ppm DES from day 13 of pregnancy increased the incidence and number of mammary carcinomas (MCs) at the earlier period while exposure to 0.1 ppm DES throughout pregnancy period enhanced the incidence and number of benign proliferative lesions (PLs) at the later period. MCs appeared earlier than benign PLs. These results suggest that exposure to DES throughout pregnancy and from day 13 of pregnancy could induce endocrine disrupting conditions and enhance the induction of MCs and that exposure to DES throughout pregnancy enhance PLs.