The objective of this research project is to elucidate the photochemical and photobiological mechanisms whereby light (UVA and visible radiation) alone or in the presence of endogenous or exogenous photosensitizers exerts either toxic or therapeutic effects. UVA-induced apoptosis in keratinocytes is associated with EGF receptor internalization and down-regulation without receptor phosphorylation and ubiquitination; also UVA exposure causes delayed and sustained activation of ERK MAP kinase. We have identified the skin lipid cholesta-5,7,9(11)-trien-3 beta-ol (9-DDHC) as the putative agent responsible for UVA-induced skin photosensitivity in Smith-Lemli-Opitz syndrome patients. 9-DDHC generates singlet oxygen and superoxide upon UVA irradiation and is phototoxic to keratinocytes. A2E, a lipid degradation product found in lipofuscin granules deposited in the retina, is photoprotective in the young eye but may be phototoxic in older eyes. Phloxine B, a red dye used in cosmetics and as a phototoxin for the control of fruit flies, generates singlet oxygen and superoxide upon visible irradiation and is phototoxic to keratinocytes

National Institute of Health (NIH)
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
Chignell, C F; Han, S-K; Mouithys-Mickalad, A et al. (2008) EPR studies of in vivo radical production by 3,3',5,5'-tetrabromobisphenol A (TBBPA) in the Sprague-Dawley rat. Toxicol Appl Pharmacol 230:17-22
He, Yu-Ying; Council, Sarah E; Feng, Li et al. (2008) Spatial distribution of protein damage by singlet oxygen in keratinocytes. Photochem Photobiol 84:69-74
Han, S K; Bilski, P; Karriker, B et al. (2008) Oxidation of flame retardant tetrabromobisphenol A by singlet oxygen. Environ Sci Technol 42:166-72
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
He, Y-Y; Pi, J; Huang, J-L et al. (2006) Chronic UVA irradiation of human HaCaT keratinocytes induces malignant transformation associated with acquired apoptotic resistance. Oncogene 25:3680-8
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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