ULTRAVIOLET LIGHT INDUCED PHENOMENA IN BIOMEMBRANES

描述(改编自申请者的摘要)：远景目标 本应用程序的目的是了解基本的光化学和 将药物光毒性反应降至最低所需的光生物学过程 为膜的合理应用设计新的药物和方法 医学和生物学中的光敏化。此应用程序有两个 具体目标：(1)膜中的活性物种 光敏作用及其对生化变化的形成部位 产生于细胞质膜并引起细胞功能的变化。这 基本信息可用于光化学设计染料。 开始治疗，并解释光毒性药物的影响。 单线态氧或芳基/卤化物的膜光敏化 从光毒药物中产生的自由基将通过测量 质膜电位、主动转运和膜的变化 角质形成细胞和骨髓单核细胞系的通透性。影响 光敏剂的位置将通过创建相同的 膜内外的活性物种和通过生成 膜内相同位置的不同活性物种。这个 膜损伤机制与细胞周期变化的关系 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，以及抗原提呈的抑制。(2)确定 高强度激光辐射影响生物多样性的机制 膜的光敏效率。使用高强度辐射 可以改变光敏效率，并引入非氧依赖 机械装置。这些效应可能在低氧的光动力疗法中有用。 肿瘤区域和其他光敏治疗。这个 将在辐射强度和产量之间建立关系 在光敏剂激发态中，光子的后续吸收 激发态和活性物种的产率。光物理 研究将在脂质体和红细胞中使用孟加拉玫瑰和花青素540 膜。预测强度依赖的治疗效率的能力 将测试来自光物理测量的光敏化。 光生物学研究将测量红细胞的光敏抑制 黄曲霉毒素对白血病细胞膜酶活性及细胞毒作用的研究 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.