ULTRAVIOLET LIGHT INDUCED PHENOMENA IN BIOMEMBRANES

光敏化膜损伤是导致皮肤 某些药物的光毒性，并可用于治疗，如果 光敏作用针对异常组织。 这些目标 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)为了确定三种光毒性化合物的光化学是否在 溶液和脂质体中的浓度可用于预测膜 药物的光敏化能力。 光化学机制 胺碘酮、苯恶洛芬和吡罗昔康的光毒性代谢物将被 使用动力学和淬灭研究以及产物分析确定。 膜损伤的终点将包括裂解和共价交联 膜蛋白使用红细胞，酶抑制，损失 膜完整性和使用人二倍体的药物结合抑制 成纤维细胞 2)确定潜在光引发肿瘤的机制 基于线粒体内的花青染料光敏化的疗法 膜的 染料的可能位置将使用 吸收和荧光以及放射性标记的染料。 的 染料光敏化抑制电子传递中的特定步骤， 将评估氧化磷酸化的磷酸化反应。 可能的分子光化学机制将进行评估，包括 染料与蛋白质的共价结合，膜组分的氧化，以及 涉及染料的有毒光产物。 的结果予以 研究将用于合理设计具有最佳定位的染料， 光敏能力。

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.