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. Numerous health disparities exist in the rural population of Mississippi; e. g. Mississippi leads the nation in deaths from cardiovascular disease. The cause of the health disparities is likely multifactorial. Environmental factors are likely to account for some of this disparity. Mississippians are continually exposed to low levels of various pesticides including those in current use as well as legacy pesticides, those used in the past but still present in the environment today. One legacy pesticide of particular concern is dieldrin. Dieldrin has been shown to influence the expression of many genes coding for physiologically important proteins including cytochrome P450 enzymes (CYPs) and transport proteins. However, the effect of dieldrin on gene transcription at environmentally relevant concentrations is poorly understood. Thus the effect of dieldrin on Mississippians health is not known. In this pilot project, we will determine the effect of low dose dieldrin treatment on the in vivo expression of 3 rat carboxylesterase enzymes, rat hydrolase A, B, and S, and on the expression of 2 transport proteins, rat multidrug resistance-associated protein 2 (MRP2) and organic anion transport polypeptide 2 (OATP2). Carboxylesterase enzymes are involved in the metabolism of many drugs and recently have been implicated in cholesterol metabolism. MRP2 and OATP2 are involved in bile acid metabolism, multidrug resistance, and cholesterol metabolism. A more complete understanding of dieldrin s effects on gene expression will enable us to better assess the role of dieldrin in the health disparities experienced by Mississippians.
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