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.

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National Institute of Environmental Health Sciences (NIEHS)
Intramural Research (Z01)
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U.S. National Inst of Environ Hlth Scis
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Wiechmann, Allan F; Chignell, Colin F; Roberts, Joan E (2008) Influence of dietary melatonin on photoreceptor survival in the rat retina: an ocular toxicity study. Exp Eye Res 86:241-50
Roberts, Joan E; Wielgus, Albert R; Boyes, William K et al. (2008) Phototoxicity and cytotoxicity of fullerol in human lens epithelial cells. Toxicol Appl Pharmacol 228:49-58
He, Yu-Ying; Council, Sarah E; Feng, Li et al. (2008) UVA-induced cell cycle progression is mediated by a disintegrin and metalloprotease/epidermal growth factor receptor/AKT/Cyclin D1 pathways in keratinocytes. Cancer Res 68:3752-8
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Chignell, Colin F; Sik, Robert H; Watson, Mary A et al. (2007) Photochemistry and photocytotoxicity of alkaloids from Goldenseal (Hydrastis canadensis L.) 3: effect on human lens and retinal pigment epithelial cells. Photochem Photobiol 83:938-43
Wielgus, Albert R; Chignell, Colin F; Miller, David S et al. (2007) Phototoxicity in human retinal pigment epithelial cells promoted by hypericin, a component of St. John's wort. Photochem Photobiol 83:706-13
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Matsumoto, Ken-ichiro; Kawai, Sayo; Chignell, Colin F et al. (2006) Location of anthralin radical generation in mouse skin by UV-A irradiation: an estimation using microscopic EPR spectral-spatial imaging. Magn Reson Med 55:738-42

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