NUTRITIONAL REGULATION OF CARCINOGENS IN PLACENTA-RELATED CELLS

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The plasma membrane glycoprotein 170 (P-gp) responsible for multidrug resistance, MDR, also may function as a efflux pump for chemical carcinogens and 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. We have determined that P-gp mRNA may be developmentally regulated in human placental tissues. Currently, a developmental study in rats is in progress to examine P-gp expression in normal tissues during pregnancy. In addition, several newly developed rat placental cell lines (prepared by J. Y. Chou) are being tested as in vitro models. The regulation of expression of MDR by nutrients in these placenta-related cell lines will be studied. We are also examining the expression of mdr1 and mdr3 in human in vitro models, two cervical carcinomas, an endometrial adenocarcinoma, and an ovarian adenocarcinoma. Regulatory agents such as progesterone, estradiol, and benzo(a)pyrene, and nutrients such as sodium butyrate, retinoic acid, dexamethasone, and dibutyryl cAMP are being examined for regulatory roles in the expression of MDR and the prevention of carcinogenesis.