MECHANISMS OF CHEMICALLY INDUCED PHOTOSENSITIVITY

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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.