GLUTATHIONE S TRANSFERASE & ITS REGULATION OF CARCINOGENIC ELECTROPHILES

我们正在研究谷胱甘肽S-转移酶及其调节 致癌亲电体。 脂质体介导的rGST递送 谷胱甘肽S-转移酶可用于保护胃肠道 细胞 我们目前的努力是针对交付 将GST分子强制进化到上皮细胞， 使用合成脂质体的上消化道的lurnen。 一些脂质体 正在优化的参数包括：尺寸/内部。 音量， 外膜电荷，存在外膜对接 分子，外膜的涂层，以抑制脂肪酶 降解，脂质的pH敏感性，以促进脂质体溶解 在核内体中，以及重组分子在核内体中的存在， 脂质体内容物以促进内体的破坏和脂质体的递送。 脂质体内容物到胞质溶胶中。 上消化道一过性强化 具有rGST/GSH的细胞可以提供保护这些细胞的手段 在使用短半衰期氮的全身癌症化疗期间 吗啡，如美法仑、环磷酰胺或苯丁酸氮芥。 我们 目前，初步的实验涉及治疗组织中的GI细胞， 培养，其中细胞粘附在盖玻片上，然后进行处理 用脂质体悬浮液。 我们的目标是研究脂质体粘附 以及脂质体内容物沉积到培养的细胞中。 我们计划 使用共聚焦显微镜来监测分子进入 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.