Mechanisms Of Chemically Induced Photosensitivity

化学诱导光敏性的机制

• 批准号: 6672981
• 负责人: COLIN CHIGNELL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6672981
• 关键词: DNA damage; antibacterial agents; carcinogen testing; drug screening /evaluation; environmental exposure; hairless mouse; mutagen testing; photoactivation; photochemistry; photosensitizing agents; radiation carcinogen; radiation carcinogenesis; radiation hazard; radiobiology; singlet oxygen; ultraviolet radiation

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.

工作摘要：当紫外线或可见光与皮肤和眼睛中的内源性或外源性化学剂相互作用时，可以产生光敏性。这个过程可能会产生不良的临床后果，例如光毒性（夸张的晒伤），光含量，光钙化性和/或光毒素；或者它可能具有有益的作用，例如肿瘤光动力疗法（PDT）和煤焦油，静脉素或8-甲氧基索拉伦（PUVA）治疗牛皮癣。该研究项目的目的是阐明光化学机制，即在存在或不存在光敏剂的情况下光（紫外线或可见）发挥其毒性作用。我们发现，暴露于DNA片段化电泳和流式细胞仪确定的24小时后，UVA辐射导致皮肤细胞（角质形成细胞）的编程细胞死亡（凋亡）。 Juglone是黑核桃中存在的化学物质，是饮食补充剂，染发剂和核桃油污渍的组成部分。有时将碎的黑胡桃壳施加在皮肤上，以治疗真菌，细菌或病毒感染。 Juglone目前正在国家毒理学计划进行研究。我们发现朱隆对皮肤细胞（角质形成细胞）有毒，后者将其转换为高反应性和有毒的自由基。酮普罗芬是一种广泛使用的非甾体类抗炎药（NSAID），在UVA辐照后引起光毒性和光含量，在UVA辐照后诱导诱导非母胆红蛋白，羟苯甲酰金蛋白质，肌球蛋白，肌球蛋白和红细胞的蛋白质自由基的形成。我们已经测试了TG.AC小鼠检测光碳纤维菌素（在光照下引起皮肤癌的化学物质）的能力，并发现该转基因小鼠对紫外线/8-甲氧基索拉伦有反应，但对UV/lomefloxacin却不敏感。