Abstract

Light is known to interact with endogenous or exogenous chemical agents in the skin or eyes, to produce photosensitization. This phenomenon may be deleterious (phototoxicity or photoallergy) or may be useful therapeutically (photodynamic treatment of psoriasis or tumors). The objective of this project is to determine the role played by light- induced free radical species in photosensitization. In addition, efforts are directed towards the identification of photosensitizers that may be more efficient therapeutically. 1,5-Diamino-4,8-dimethoxy-anthraquinone and related analogs were efficient generators of both O2 and 1O2 upon visible light illumination. These compounds were active against K562 human chronic myeloid leukemic cells in culture causing frank strand breaks in DNA. Anthrapyrazoles, which are also potential photodynamic agents, become strong oxidizers upon illumination with visible light. UV-irradiation of N-hydroxy-2-thiopyridine, an anti-bacterial and anti- fungal agent, generated the hydroxyl radical and the corresponding N- hydroxy-2-pyridine thiyl radical.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES050046-15
Application #
3777527
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
National Institute of Environmental Health Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

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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