This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. NOTE: Tables and Figures were uploaded with the Overall Research Summary file. BACKGROUND The polycyclic aromatic hydrocarbon (PAH) family includes 100 different compounds one of them being benzo(a)pyrene (BaP). These compounds are formed from natural and synthetic sources that involve high-temperature pyrolytic processes, however, PAHs originating from synthetic sources are quantitatively more distributed in the environment. Sources of human exposures, albeit not an exhaustive list, include: home heating and cooking with coal or wood, cigarette smoke, automobile exhaust emissions, contaminated foods, manufacturing industries for coke, graphite-electrode and carbon-anode. The steric resemblance of BaP and their metabolites to E2 confers estrogenic and antiestrogenic activity to these molecules. Estrogenic effect of BaP is exemplified in its ability to promote the proliferation as well as the alteration of E2 metabolism of human mammary terminal duct cell cultures. On the contrary, BaP and other PAHs exhibit their antiestrogenic activity by decreasing circulating levels of E2. The reduction in circulating E2 could occur either by BaP-induced decreases in the synthesis and release of E2 or via the enhancement of E2 metabolism by liver cytochrome P-450 enzyme. The ultimate result of the reduction in E2 is the reduction of E2 receptor synthesis and E2 mediated biological function particularly in the ovaries. Because of the widespread availability of PAH in the environment and the considerable probability of human exposure, the potential adverse effects of this compound the functioning of the mammalian ovary merit investigation.
SPECIFIC AIMS 1) To determine the bioavailability and toxicokinetics of benzo(a)pyrene in female rats. 2) To determine the effect of BaP treatment on plasma concentrations of gonadal steroids and the pituitary hormones that regulate these steroids during the rat estrous cycle. 3) To determine the effect of BaP on ovarian exocrine function and luteal maintenance. 4) To determine the effect of BaP on fertilization and pre-implantation development.
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