Effects of neonatally administered low-dose diethylstilbestrol on the induction of mammary carcinomas and dysplasias induced by 7,12-dimethylbenz [a] anthracene in female rats.

The aim of this study was to investigate the effects of neonatal administration of diethylstilbestrol (DES) on the induction of mammary carcinomas (MCs) and dysplasias (MDs) induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female rats. Three different methods of continuous administration of DES (1 microg) were used: 0-14, 0-5 and 6-14 days after birth, and all rats were given DMBA (10 mg) at 50 days after birth. All rats administered DES showed persistent estrus and anovulatory ovaries. In rats administered DES from 0-14 days after birth, neither MCs nor MDs were observed, and serum levels of both estrogen and progesterone were significantly lower than in controls at 100 days after birth. In rats administered DES from 0-5 days after birth, the incidence and number of MCs were significantly lower while the number ofMDs was slightly higher than in controls. In rats administered DES from 6-14 days after birth, the incidence of MCs was equal to that of the controls while the incidence and number ofMDs were significantly higher. These results suggest that neonatal periods of exposure and doses of endocrine disruptors, such as DES, could affect the incidence and progression of MCs and MDs.

Effects of neonatal administration of diethylstilbestrol on aberrant crypt foci induced by 7,12-dimethylbenz[alpha] anthracene in rats.

Gastrointestinal carcinoma is affected environmental factors, however, it remains to be determined whether neonatal administration of an estrogenic endocrine disruptor, such as diethylstilbestrol (DES), affects gastrointestinal carcinogenesis. The effects of neonatally administered DES on gastrointestinal tumorigenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) were investigated in male and female rats. Male and female rats in group I were daily administered oil alone from 0-14 days after birth. Male and female rats in groups II and III were daily administered DES at 1 and 10 microg/rat, respectively. The administration periods of DES in subgroups a (IIa and IIIa), b (IIb and IIIb) and c (IIc and IIIc) were from 0-14, 0-5 and 6-14 days after birth, respectively. At 28, 42 and 56 days after birth, all male rats were given 10 mg of DMBA. At 50 days after birth, all female rats were given 10 mg of DMBA. In the digestive tracts of male rats, forestomach masses (FMs) in all groups (13-58%), small intestine masses in group IIIa (17%), and colon masses (CMs) in groups IIIa (8%) and IIIb (33%) were observed, although there were no significant changes in the incidence and number. In the digestive tracts of female rats, FMs in groups I (10%), IIa (13%), IIb (33%), IIc (25%) and IIIc (33%), CMs in groups IIa (6%) and IIIa (6%) were seen, although there were no significant changes in the incidence. Aberrant crypt foci (ACF) in the colon and rectum were seen in all male and female rats. The neonatal administration of DES in male rats increased the number of ACF while that in female rats did not. These results suggest that neonatal administration of DES may affect male colorectal carcinogenesis.

Increased bone mineral density in aged rats with spontaneous mammary dysplasia.

Spontaneous mammary tumors were seen in seven of the 12 breeding female rats aged 2 years. All mammary tumors were diagnosed as mammary dysplasia (MD). Bone mineral contents (BMC) and bone mineral density (BMD) of their lumbar vertebrae and femur were determined using dual energy X-ray absorptiometry (DXA). In rats with MD, body weight (BW), BMD of the lumbar vertebrae and BMC of the femur were significantly higher than in the rats without MD. Although corpus luteum (CL) and follicles were seen in the ovaries of all animals, the number of CL in rats with MD was significantly lower than the rats without MD. It was suggested that high BMD, BW and decreased CL promoted mammary tumors.

Expression of estrogen receptor-alpha protein in the rat digestive tract.

The current study evaluates the expression of estrogen receptor-alpha (ER-alpha) protein in the digestive tract and other organs using immunohistochemistry in male and female intact rats. As a result, the expression of ER-alpha protein was intensively immunoreactive in the nuclei of squamous epithelium of the forestomach connected to the limiting ridge and the anus connected to the anorectal junction. Rat ER-alpha mRNA signals were also detected in the epithelium of the limiting ridge using in situ hybridization. The incidence of ER-alpha protein in the limiting ridge decreased with age in both males and females. The incidence of ER-alpha protein in the anorectal junction strongly decreased with age in males, although the incidence did not decrease with age in females. In conclusion, it was suggested that estrogen may be involved in the proliferation and differentiation of these cells in the limiting ridge of the stomach and anorectal junction of rats.

Effects of neonatally-administered 17beta-estradiol on induction of mammary carcinomas by 7, 12-dimethylbenz[a]anthracene in female rats.

Various doses of 17beta-estradiol (E2) were administered subcutaneously to inbred female Sprague-Dawley (SD) rats once at birth. At 50 days after birth, rats in all the groups were given 10 mg of 7, 12-dimethylbenz[a]anthracene (DMBA). In the 1000 microg group, the incidence and number of mammary carcinomas were markedly low, while in the 10 microg group, a large number of mammary carcinomas was noted. Corpora lutea were observed in all rats in the control, 0.1, 1, 10 and 100 microg groups at 50 days old; however, no corpora lutea were observed in any rat in the 1000 mg group at age 50 days and at sacrifice. Observation of the whole-mount specimens showed a low number of terminal end buds (TEBs) in the 1000 microg group and a high number in the 10 microg group. It is suggested that neonatal administration of E2 affects the gonadotropin-secreting system, resulting in a decrease of progesterone, which is thought to influence the progression of mammary carcinomas induced by DMBA. Moreover, neonatal administration of E2 directly affects the mammary glands, and it is suggested that E2 may promote differentiation of TEBs resulting in inhibitory effects on the initiation of mammary carcinomas.