• Influence of Benzo(a)pyrene (BaP) on Ovarian Function (Pilot)

            Anthony E. Archibong, Ph.D. and Aramandla Ramesh, Ph.D.
Data from the National Center for Health Statistics indicate that the number of women with an impaired ability to have children is about 6.1 million and growing. Most of these infertility cases are idiopathic and therefore may originate from environmental exposure to xenobiotics including BaP. Using adult female rats exposed to BaP, this study will determine the bio availability and toxicokinetics of BaP and the effect of BaP treatment on: a) plasma concentrations of gonadal steroids and the pituitary hormones that regulate these steroids during the rat estrous cycle; b) ovarian function and luteal maintenance; and c) fertilization and pre-implantation development.

• Human Mammary Stroma as Target for Organochlorines (Pilot)

            Sakina Eltom, D.V.M, Ph.D.
Environmental organochlorines such as PCBs and DDT may not only confer an increased risk of breast cancer among young African American women but may also yield a more aggressive form of the disease. Using an in vitro cell culture system of human mammary epithelia plus stromal fibroblasts from African American and white women donors, this proposal will: a)  characterize the heterogeneity of breast epithelia and fibroblasts with respect to their estrogen-responsiveness and how they are modified by exposure to organochlorines; b) verify that activation of estrogen receptors by organochlorines affects expression of stromal growth factors; and c) identify those stromal factors expressed in response to estrogens and their modification by organochlorines using microarray and protein expression profiling. 

• Dissecting COX-1 Related Gene Pathways in Ovarian Cancer (Pilot)

            Dineo Khabele, M.D.
The prostaglandin pathway mediated by cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes is implicated in ovulation and has been suggested as a potential factor in the etiology of ovarian cancer. This study will monitor expression levels of COX-1, COX-2 and molecular markers associated with the PI-3 kinase/Akt signaling pathway [hypoxia induced factor (HIF-1α) and vascular endothelial growth factor (VEGF)] in human ovarian tissue samples using tissue microarrays. Parallel in vitro experiments will further evaluate COX-1 function by treating an ovarian cancer cell line, OVCAR3, with a selective COX-1 inhibitor, SC-560, and using cDNA microarrays to generate gene profiles that are associated with COX-1 activation.  Should COX-1 prove to be a prominent factor in tumor progression in ovarian cancer, this research may provide the basis for its future use as a bio marker and therapeutic target for management of this deadly disease.