Mechanisms Of Chemically Induced Photosensitivity

工作概述：当紫外线或可见光与皮肤和眼睛内的内源性或外源性化学物质相互作用时，会产生光敏。这一过程可能产生不良的临床后果，如光毒性（过度晒伤）、光过敏、光致癌性和/或光致突变性；或者在肿瘤光动力治疗（PDT）和煤焦油、蒽醌或8-甲氧基补骨脂素（PUVA）治疗牛皮癣中有有益的效果。本研究项目的目的是阐明光（紫外线或可见光）在存在或不存在光敏剂的情况下发挥其毒性作用的光化学机制。我们发现，通过DNA片段电泳和流式细胞术检测，UVA照射在暴露24小时后引起皮肤细胞（角质形成细胞）的程序性细胞死亡（凋亡）。核桃酮是一种存在于黑核桃中的化学物质，是膳食补充剂、染发剂和核桃油渍的一种成分。压碎的黑核桃壳有时用于皮肤治疗真菌、细菌或病毒感染。目前，国家毒理学计划正在对Juglone进行研究。我们发现核桃酮对皮肤细胞（角质形成细胞）有毒，使其转化为高活性和有毒的自由基。酮洛芬是一种广泛使用的非甾体抗炎药（NSAID），可引起光毒性和光过敏，在UVA照射下，可诱导高铁血红蛋白、氧合血红蛋白、肌红蛋白和红细胞中形成蛋白质自由基。我们已经测试了Tg的能力。AC小鼠检测光致癌物（在光线下引起皮肤癌的化学物质），发现这种转基因小鼠对UV/8-甲氧基补骨脂素有反应，但对UV/洛美沙星不敏感。

Summary of work: Photosensitization can result when UV or visible light interacts with endogenous or exogenous chemical agents in the skin and eyes. This process can produce undesirable clinical consequences, such as phototoxicity (exaggerated sunburn), photoallergy, photocarcinogenicity and/or photomutagenicity ; or it can have beneficial effects as in tumor photodynamic therapy (PDT) and coal tar, anthralin or 8-methoxypsoralen (PUVA) therapy for psoriasis. The objective of this research project is to elucidate the photochemical mechanisms whereby light (UV or visible) in the presence or absence of photosensitizers exerts its toxic effect. We have found that UVA irradiation caused programmed cell death (apoptosis) of skin cells (keratinocytes) 24 hours after exposure as determined by DNA fragmentation electrophoresis and flow cytometry. Juglone, a chemical present in black walnuts, is a component of dietary supplements, hair dyes and walnut oil stains. Crushed black walnut hulls are sometimes applied to the skin to treat fungal, bacterial or viral infections. Juglone is currently undergoing study by the National Toxicology Program. We have found that juglone is toxic to skin cells (keratinocytes), which convert it to highly reactive and toxic free radicals. Ketoprofen, a widely used non-steroidal anti-inflammatory drug (NSAID) that causes both phototoxicity and photoallergy, upon UVA irradiation, induced the formation of protein radicals in methemoglobin, oxyhemoglobin, myoglobin and red blood cells. We have tested the ability of the Tg.AC mouse to detect photocarcinogens (chemicals that cause skin cancer in the presence of light) and found that while this transgenic mouse responds to UV/8-methoxypsoralen, it is not sensitive to UV/lomefloxacin.