NUTRITIONAL REGULATION OF CARCINOGENS IN PLACENTA-RELATED CELLS

多药相关的质膜糖蛋白170(P-gp) 抗性，MDR，也可以作为化学物质的外排泵 它是致癌物质，可以通过饮食和营养来调节。发现P-gp 主要分布在管腔间隙内的各种正常细胞 组织，包括胎盘和妊娠子宫的子宫内膜。 P-gp在正常组织中的功能作用尚未确定。 然而，我们最近的发现表明，P-gp mRNA是发育中的 在人类胎盘组织中受到调控。目前，一项发展研究在 大鼠孕期正常组织中P-gp的表达正在进行中。 大鼠胎盘、卵巢、子宫、肾上腺和肾脏 妊娠18天正在处理P-gp在mRNA的表达 和蛋白质水平。此外，SV40温度敏感型A(TSA)大鼠 胎盘细胞系被用来检测营养物质和饮食的影响 影响P-gp调控的因素。 阿霉素耐药大鼠胎盘细胞系的建立 检测P-gp在防御致癌物中的作用的模型。我们 将研究营养物质和致癌物对野生型P-gp的调节 以及耐药胎盘细胞在蛋白质和mRNA水平的表达。在……里面 此外，我们正在研究P-gp在人类子宫内膜中的调节。 腺癌细胞系和人宫颈癌细胞系。膳食 如维甲酸等已知可增强P-gp表达的效应物，以及 黄酮类，山奈酚，正在研究在人类子宫内膜和 宫颈细胞系。特别关注两种形式的多药耐药 MDR基因(MDR-1和MDR-3)及其在饮食中的差异调控 因素和致癌物，以了解生理调节 P-gp。

The plasma membrane glycoprotein 170 (P-gp) responsible for multidrug resistance, MDR, also may function as an 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 normal tissues, including the placenta and the endometrium of the gravid uterus. The functional role of P-gp in normal tissues has not been determined. However, our recent findings indicate that P-gp mRNA is developmentally regulated in human placental tissues. Currently, a developmental study in rats of P-gp expression in normal tissues during gestation is in progress. Rat placentas, ovaries, uteri, adrenals and kidneys at 0, 6, 9, 12, 15 and 18 days of gestation are being processed for P-gp expression at the mRNA and protein levels. In addition, a SV40-temperature sensitive A (tsA) rat placental cell line is used to examine the effects of nutrients and diet factors in P-gp regulation. A doxorubicin-resistant rat placental cell line has been established as a model for examining P-gp function in the defense against carcinogens. We will study the regulation of P-gp by nutrients and carcinogens in wild-type and drug-resistant placental cells at the protein and mRNA levels. In addition, we are studying the regulation of P-gp in a human endometrial adenocarcinoma cell line and a human cervical carcinoma cell line. Dietary effectors such as retinoic acid, known to enhance P-gp expression, and the flavonoid, kaempferol, are being investigated in the human endometrial and cervical cell lines. Special attention is paid to the two forms of MDR genes (mdr 1 and mdr 3) and their differential regulation by dietary factors and carcinogens in order to understand the physiologic regulation of P-gp.