Cell membrane alterations are involved in several harmful and beneficial dermatological responses to ultraviolet (UV, 200-400 nm) and visible (400-700 nm) radiation, including sunburn, solar urticaria, drug phototoxicity and photochemotherapy. Visible, UVA (320-400 nm) and UVB (290-320 nm) radiation are part of the solar spectrum to which man is exposed. The long-term objectives of this research are to determine the molecular mechanisms for photoinitiated cell membrane damage and to apply this knowledge to the development of new photochemotherapies and treatments for cutaneous photosensitivity. Specifically, the research aims are: 1) To determine the mechanisms for the photochemical reactions of cell membrane components by investigating the UVB-initiated reactions fo peptides and phospholipids in aqueous and nonaqueous solution and in liposomes; 2) To study cutaneous phototoxic compounds and their mechanisms for membrane damage. Basic photochemical studies will be made on chlorpromazine, protriptyline, benoxaprofen and coal tar components in solution, in liposomes and in red blood cell membranes. The membrane photosensitizing effectiveness of chromophores which are covalently linked to antibodies will be evaluated; 3) To determine the mechanisms of photobiologic effects on mast cells and lymphocytes in the presence and absence of photosensitizers. Mast cell degranulation will be monitored as a function of wavelength and dose of UV radiation in the presence and absence of photosensitizers. The mechanism whereby membrane-specific photosensitizers decrease the blastogenic response of lymphocytes to a mitogen will be investigated. The results of these studies will be applied to modifying photobiologic responses in skin and to optimizing the therapeutic benefits of photochemotherapies. The knowledge gained from studies of phototoxicity mechanisms can be used to predict potential photosensitizers, suggest modifications to reduce their photosensitizing potential, and to generate new photochemotherapeutic agents.
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