ULTRAVIOLET LIGHT INDUCED PHENOMENA IN BIOMEMBRANES

光敏膜损伤是皮肤损伤的原因 某些药物的光毒性，可用于治疗如果 光敏作用针对的是异常组织。我们的目标是 预测药物的光敏潜力并开发治疗方法 基于体内光化学。这些目标需要了解 光敏化的分子机制。具体目标是： 1)确定三种光毒化合物的光化学是否 溶液和脂质体可以用来预测膜 药物的光敏能力。光化学作用的机理 胺碘酮、苯扎洛芬和吡罗昔康的光毒性代谢物将是 使用动力学和猝灭研究以及产品分析来确定。 膜损伤的终点包括裂解和共价交联。 利用红细胞膜蛋白，和酶的抑制，损失 使用人二倍体的膜完整性和药物结合的抑制 成纤维细胞。 2)确定潜在的光引发肿瘤的机制(S) 基于菁染料光敏化内线粒体的治疗 薄膜。染料的可能位置将使用以下方法确定 吸收、荧光和放射性标记的染料。这个 染料光敏抑制电子传递和运输中的特定步骤 将对氧化磷酸化的磷酸化反应进行评估。 可能的分子光化学机制将被评估，包括 染料与蛋白质的共价结合，膜成分的氧化，以及 涉及有毒感光产品的染料。这些研究的结果 研究将用于合理设计具有最佳局部化和 感光能力。

Photosensitized membrane damage is responsible for the cutaneous phototoxicity of certain drugs and can be used for therapy if the photosensitization is directed to abnormal tissue. The goals are to predict the photosensitizing potential of drugs and to develop therapies based on in vivo photochemistry. These goals require understanding of the molecular mechanisms for photosensitization. The specific aims are: 1) To determine whether the photochemistry of three phototoxic compounds in solution and in liposomes can be used to predict the membrane photosensitizing ability of the drugs. The photochemical mechanisms for amiodarone, benoxaprofen and the phototoxic metabolite of piroxicam will be determined using kinetic and quenching studies and product analysis. Endpoints for membrane damage will include lysis and covalent crosslinking of membrane proteins using red cells, and enzyme inhibition, loss of membrane integrity, and inhibition of drug binding using human diploid fibroblasts. 2) To determine the mechanism(s) for a potential light-initiated tumor therapy based on cyanine dye photosensitization of the inner mitochondrial membrane. The probable locations for the dyes will be determined using absorption and fluorescence and radioactivity labelled dyes. The dye-photosensitized inhibition of specific steps in electron transport and phosphorylation reactions of oxidative phosphorylation will be assessed. Possible molecular photochemical mechanisms will be evaluated including covalent binding of dye to proteins, oxidation of membrane components, and involvement of toxic photoproducts of the dye. The results of these studies will be used to rationally design dyes with optimal localizing and photosensitizing abilities.