GLUTATHIONE S TRANSFERASE & ITS REGULATION OF CARCINOGENIC ELECTROPHILES

我们正在研究谷胱甘肽S转移酶及其对 致癌的亲电体。脂质体介导人重组谷胱甘肽转移酶 谷胱甘肽S转移酶可用于保护胃肠道 细胞。我们目前的努力是为了交付 强迫进化的GST分子到排列在 使用合成脂质体进行上消化道的潜伏。一些脂质体 正在优化的参数包括：尺寸/内部。音量， 外膜充电，存在外膜对接 分子，覆盖在外膜上以抑制脂肪酶 脂类的降解、pH敏感性促进脂质体的溶解 以及重组分子在内体中的存在 脂质体内容物促进内容体的破坏和递送 脂质体内容物以胞浆形式存在。上消化道的瞬时防御工事 含有RGST/GSH的细胞可以提供一种保护这些细胞的手段 短半衰期氮素全身化疗中的应用 芥末，如马法兰、环磷酰胺或百菌清。我们的 目前，最初的实验涉及治疗组织中的胃肠道细胞 将细胞贴在盖片上然后进行处理的培养 用脂质体混悬液。我们的目标是研究脂质体的依从性 以及脂质体内容物沉积到培养细胞中。我们计划 使用共聚焦显微镜监测分子在体内的传递 上皮细胞。

We are studying glutathione S-transferase and its regulation of carcinogenic electrophiles. Liposome-mediated delivery of rGST (glutathione S-transferase) may be used to protect gastrointestinal cells. Our current effort is directed toward the delivery of forced-evolution GST molecules to the epithelial cells which line the lurnen of the upper GI tract using synthetic liposomes. Some liposome parameters that are being optimized include: size/internal. volume, external membrane charge, presence of external membrane docking molecules, coating of the external membrane to inhibit lipase degradation, pH sensitivity of lipids to foster liposome dissolution in endosomes, and the presence of recombinant molecules in the liposome contents to foster-breakage of endosomes and delivery of the liposome contents to cytosol. Transient fortification of upper-GI cells with rGST/GSH could provide a means to protect these cells during systemic cancer chemotherapy with short half-life nitrogen mustards such as melphalan, cyclophosphamide or chlorambucil. Our current, initial experiments involve treating GI cells in tissue culture where the cells are adhered to cover slips and then treated with liposome suspensions. Our goal is to study liposome adherence and deposition of liposome contents into the cultured cells. We plan to use confocal microscopy to monitor delivery of molecules into epithelial cells.