MECHANISMS OF TCDD-INDUCED DEVELOPMENTAL ALTERATIONS

University Of North Carolina Chapel Hill, Chapel Hill NC

Investigators

Abstract

DESCRIPTION 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant demonstrated to cause numerous responses including altered sexual development. The World Health Organization recently stated that levels of dioxins in the environment result in body burdens in the background population that are near the level where adverse effects might be expected to occur. Furthermore, the developing embryo/fetus appears to be the most susceptible lifestage across a wide range of species Among the alterations noted, TCDD has been show shown to impair epithelial development of several reproductive tract tissues (prostate, mammary gland and seminal vesicles). This proposal seeks to better define this alteration in the rat seminal vesicles following in utero and lactational exposure to TCDD. Once the lesion is characterized histologically, it is the goal of this proposal to begin to understand the mechanism underlying alterations by examining the expression of the transcriptional machinery involved in TCDD signaling, growth factor expression and use gene microarray technology to search for additional changes in gene expression. These studies will lead to a better understanding of TCDD- induced epithelial alterations. This information can in turn be used to understand the human health risk associated with body burdens in the background population.