LB-111

Commonly known as dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been recognized as a potent human carcinogen, yet it remains ubiquitous in the environment as a byproduct of incineration procedures and waste disposal. It is a well-studied, endocrine- disrupting chemical that alters cellular organization at both macroscopic and molecular levels. In this study, the goal was to determine the modulatory effects that prenatal TCDD exposure has on uterine morphology, cell proliferation, apoptosis, and protein expression in an in vivo model. Pregnant Sprague-Dawley rats were treated with 3 μg TCDD/kg body weight by gavage on gestational day 15. Female offspring were sacrificed at 21 and 50 days postpartum, and uteri were dissected out for processing and analysis. Hematoxylin and eosin stains were used to compare uterine morphology between groups. Western blot, cell proliferation, and apoptosis analyses were used to assess the differences between the control and TCDD-treated animals at both 21 and 50 days of age. At 50 days postpartum, there was a striking alteration in uterine morphology between the groups. Rats treated with TCDD in utero displayed uteri that were atrophic with decreased branching compared to the controls. Though atrophic in appearance, the uteri of TCDD-exposed rats demonstrated a significant increase in epithelial cell proliferation and a decrease in apoptosis. Proteins known to play significant roles in uterine growth and disease development were also modulated by TCDD treatment, including EGFR, IGF-BP3, and SOD1. We conclude that TCDD can inhibit maturation and modulate uterine proteins that are known to play a role in uterine growth and disease as well as alter epithelial cell proliferation and apoptosis in a manner that may enhance disease, including carcinogenesis, susceptibility

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA