ULTRAVIOLET LIGHT INDUCED PHENOMENA IN BIOMEMBRANES

描述（改编自申请人的摘要）：长期目标 这一应用程序是了解基本的光化学和 减少药物光毒性反应所需的光生物学过程 并设计新的药物和方法，以合理应用膜 光敏化在医学和生物学中的应用。 该应用程序有两个 具体目标：（1）涉及膜中的活性物种 光敏化及其形成部位对生化变化的影响 产生于细胞质膜和细胞功能的变化。 这 基本信息可用于设计染料， 启动治疗和解释光毒性药物的作用。 涉及单线态氧或芳基/卤化物的膜光敏化 光毒性药物产生的自由基将通过测量 质膜电位、主动转运和膜 角质形成细胞和骨髓单核细胞系的渗透性。 的影响 光敏剂的位置将通过创建相同的 反应性物种在膜内外，并通过创建 在膜内的相同位置处具有不同的反应性物质。 的 细胞膜损伤机制与细胞膜结构改变之间的关系 膜介导的细胞功能将被评估为光敏 抑制肥大细胞脱颗粒、花生四烯酸释放 角质形成细胞和抑制抗原呈递。 (2)确定 高强度激光辐射可以影响 膜光敏化效率。 使用高强度辐射 可以改变光敏效率， 机制等 这些效应可能有助于光动力学治疗缺氧 肿瘤区域和其他光敏化治疗。 的 建立了辐射强度与产量的关系 光敏剂的激发态，随后的光子吸收， 激发态和活性物质的产率。 光物理 研究将使用脂质体和RBC中的虎红和mercury 540 膜。 预测强度依赖性的效率的能力 将测试来自光物理测量的光敏性。 光生物学研究将测量RBC的光敏化抑制 膜酶活性和细胞毒性的白血病细胞系， 高激光辐射强度。

DESCRIPTION (Adapted from the applicant's abstract): The long-range goal of this application is to understand basic photochemical and photobiological processes needed to minimize drug phototoxicity responses and to design new drugs and approaches for rational application of membrane photosensitization in medicine and biology. This application has two specific aims: (1) To relate reactive species in membrane photosensitization and their site of formation to biochemical changes produced in the cell plasma membrane and to cell functional changes. This fundamental information can be used to design dyes for photochemically initiated treatments and for explaining the effects of phototoxic drugs. Membrane photosensitization involving singlet oxygen or aryl/halide radicals produced from phototoxic drugs will be compared by measuring changes in plasma membrane potential, active transport, and membrane permeability in keratinocyte and myelomonocytic cell lines. The influence of photosensitizer location will be determined by creating the same reactive species within and outside of the membrane and by creating different reactive species at the same locations within membranes. The relationship between mechanism for membrane damage and alteration of membrane-mediated cell functions will be assessed for photosensitized inhibition of mast cell degranulation, release of arachidonic acid by keratinocytes, and inhibition of antigen presentation. (2) Determine the mechanisms by which high intensity laser radiation can influence the efficiency of membrane photosensitization. Use of high intensity radiation can alter photosensitization efficiency and introduce nonoxygen-dependent mechanisms. These effects may be useful in photodynamic therapy of hypoxic regions of tumors and other photosensitization treatments. The relationship will be established between radiation intensity and the yield of photosensitizer excited states, the subsequent absorption of a photon by the excited states, and the yields of reactive species. Photophysical studies will employ Rose Bengal and merocyanine 540 in liposomes and RBC membranes. The ability to predict the efficiency of intensity-dependent photosensitization from photophysical measurements will be tested. Photobiological studies will measure photosensitized inhibition of RBC membrane enzyme activities and cytotoxicity to a leukemia cell line using high laser radiation intensities.