Effects of Neonatally Administered Diethylstilbestrol on Induction of Mammary Carcinomas Induced by 7, 12-Dimethylbenz[A]Anthracene in Female Rats

Abstract

Various doses of diethylstilbestrol (DES) were administered to rats once at birth. Thereafter, at 50 days after birth, the rats in all groups were given 10 mg 7, 12-dimethylbenz[a]anthracene (DMBA) and undergone necropsy at 300 days after birth. The incidence of mammary carcinomas (MCs) were 50, 54, 91, 39, 19% at 175 days after birth, and 77, 87, 100, 85, 75% at necropsy in the 0, 0.1, 1, 10, 100 microg groups, respectively. The incidence of rats without corpus luteum were 0, 0, 0, 30, 100% at 50 days after birth, and 0, 40, 53, 93, 100% at necropsy in the 0, 0.1, 1, 10, 100 microg groups, respectively. Observation of the whole mount specimens showed a higher number of terminal end buds (TEBs) in the 1 microg group and a lower number in the 100 microg group compared with the control at 50 days after birth. It suggested that the administration of a relatively low dose (1 microg) of DES during neonatal period may increase TEBs, thus resulting in a stimulatory effect on the initiation of MCs.

Effects of Exposure Period and Dose of Diethylstilbestrol on Pregnancy in Rats

“…The bred rats with neutrophil infiltration in the endometrium and vaginal keratosis were thought to be in pro-estrus or estrus [13]. It is possible that the strong estrogenicity of DES induced persistent estrus in the rats administered DES because rats administered DES show a high incidence of pro-estrus or estrus at necropsy and neonatal administration of a single high dose of DES and E2 induces persistent estrus in female rats [6,16]. Moreover, increased adrenal gland weights were observed in the rats treated DES.…”

“…Statistics: Statistical analyses were performed using Dr. SPSS II for Windows as described previously [10,16]. The mean differences were evaluated by Student's t-test.…”

“…However, DES is ineffective in prevention of miscarriages and premature births [4,23]. DES has also been used as a good model reagent for investigation pre-or post-natal effects of estrogenic compounds on females using animal models for human extrapolation.We have previously reported that neonatal administration of DES induced persistent estrus and an absence of corpus lutea in female rats due to disturbance of the gonadotropinsecreting system in the hypothalamus [11,16,24]. However, it remains to be determined whether the administration of DES affects pregnancy in rats.…”

“…We have previously reported that neonatal administration of DES induced persistent estrus and an absence of corpus lutea in female rats due to disturbance of the gonadotropinsecreting system in the hypothalamus [11,16,24]. However, it remains to be determined whether the administration of DES affects pregnancy in rats.…”

Gene expression profiling during rat mammary carcinogenesis induced by 7,12‐dimethylbenz[a]anthracene

“…7 The primary antibodies used were a rabbit polyclonal antibody to MMP-13 (clone: Ab-5, Lab Vision, Fremont, CA) at 1:1,000, a mouse monoclonal antibody to OPN (clone: AKm2A1, Santa Cruz Biotechnology, Santa Cruz, CA) at 1:2,000, a rabbit polyclonal antibody to MMP-7 (clone: FL-267, Santa Cruz Biotechnology) at 1:200 and the rabbit polyclonal antibody to PEP-19 at 1:100. As negative controls, a rabbit immunoglobulin fraction and mouse IgG2a immunoglobulin (DAKO Cytomation) were used for MMP-13, OPN and MMP-7 antibody and nonimmune serum (SCRUM) were used for PEP-19.…”