MECHANISMS OF CHEMICALLY INDUCED PHOTOSENSITIVITY

当光与内源性或外源性的光相互作用时， 皮肤和眼睛中的外源性化学物质。 这个过程可以产生 不良临床后果，如光毒性（夸大） 晒伤）和/或光过敏;或者它可以具有有益的效果， 肿瘤光动力疗法（PDT）和煤焦油、蒽林或补骨脂素 牛皮癣的治疗方法有哪些 本研究项目的目标是 为了阐明这些光敏剂的光化学机制， 发挥其毒性作用。 阳光已经牵连到高 在接受6-巯基嘌呤（6-巯基嘌呤）治疗的患者中发现的皮肤癌发病率 MP）以其前药硫唑嘌呤的形式。 自旋捕获研究 显示激发态6-巯基嘌呤，是一种高效的 在需氧溶液中产生超氧化物的还原剂。 在 此外，1，3（6-MP）* 可氧化抗坏血酸、甲酸和还原 谷胱甘肽 抗坏血酸和/或抗坏血酸盐浓度的降低 皮肤中的谷胱甘肽会使组织更容易受到 氧化应激 辐射嘌呤-6-磺酸，主要的6-MP 光产物，产生高度氧化性的SO 3-阴离子自由基， 可以切割DNA 因此，6-MP及其光产物和代谢产物 产生多种自由基，可能与病因有关 硫唑嘌呤诱发的皮肤癌 氟喹诺酮类（FQ）是一种 相对较新的一类抗生素，可用于治疗 革兰氏阴性细菌感染。 当用于人类时， 偶尔引起光毒性（过度晒伤）。 自从《金融时报》 含有酸性（羧基）和碱性（氨基）部分， 存在于溶液中的各种电离状态取决于pH值。 还螯合二价金属离子，例如Ca 2+和Mg 2+，其可以改性 光化学。 我们已经表征了光谱和 FQ诺氟沙星的光化学性质作为pH值的函数， 二价金属离子浓度。 生理pH下诺氟沙星 产生单线态氧和超氧化物，这可能是负责 这种药物具有光毒性。

Photosensitization can result when light interacts with endogenous or exogenous chemical agents in the skin and eyes. This process can produce undesirable clinical consequences, as in phototoxicity (exaggerated sunburn) and/or photoallergy; or it can have beneficial effects as in tumor photodynamic therapy (PDT) and coal tar, anthralin or psoralen (PUVA) therapy for psoriasis. The objective of this research project is to elucidate the photochemical mechanisms whereby these photosensitizers exert their toxic effects. Sunlight has been implicated in the high incidence of skin cancer found in patients receiving 6-mercaptopurine (6- MP) in the form of its pro-drug azathioprine. Spin trapping studies have shown that excited state 6-mercaptopurine, is a highly efficient reducing agent that in aerobic solution generates superoxide. In addition, 1,3(6-MP)* can oxidize ascorbate, formate and reduced glutathione. A decrease in the concentration of ascorbate and/or glutathione in the skin would render the tissue more susceptible to oxidative stress. Irradiation of purine-6-sulfonate, the main 6-MP photoproduct, generates the highly oxidizing SO3- anion radical, which is known to cleave DNA. Thus, 6-MP, its photoproducts and metabolites generate a variety of free radicals that may be involved in the etiology of skin cancer induced by azathioprine. Fluoroquinolones (FQ) are a relatively new class of antibiotics that are useful in the treatment of gram-negative bacterial infections. When used in humans, FQ~s occasionally cause phototoxicity (exaggerated sunburn). Since the FQ~s contain both acidic (carboxyl) and basic (amino) moieties the drugs exist in solution in a variety of ionized states depending on pH. They also chelate divalent metal ions eg Ca2+ and Mg2+ which may modify their photochemistry. We have characterized the spectroscopic and photochemical properties of the FQ norfloxacin as a function of pH and divalent metal ion concentrations. At physiological pH norfloxacin generates both singlet oxygen and superoxide which may be responsible for the drug~s phototoxicity.