NUTRITIONAL REGULATION OF CARCINOGENS IN PLACENTA-RELATED CELLS

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The plasma membrane glycoprotein 170 (P-gp) that is responsible for multidrug resistance, MDR, also may function as a chemical carcinogen efflux pump that can be regulated by diet and nutrients. P-gp is found predominantly in the cells lining the luminal space of a variety of tissues, including the placenta and the endometrium of the gravid uterus of the mouse, but the functional role of P-gp in normal tissues has not been determined. The regulation of expression of MDR by nutrients in placenta- related cell lines will be studied. We will examine the expression of MDR1 and MDR3 in in vitro models, such as a newly transformed origin-defective SV40-mutant amnion epithelial cell line, HAA580D-8C; a transformed placental trophoblast cell line; a placental fibroblast cell line; and a choriocarcinoma cell line, JEG-3. Hybridization experiments with newly developed MDR probes which are specific for MDR1 and MDR3 will soon be conducted to determine the feasibility of these cell lines as models of MDR expression. Regulatory agents such as the known MDR competitor, progesterone, the MDR enhancer, estradiol, and nutrients such as retinoic acid, dexamethasone, and dibutyrl cAMP will be examined for their regulatory roles in the expression of MDR and the prevention of carcinogenesis.