Mechanisms of psoralen photosensitization reactions

The basic aspects of cutaneous photosensitization reactions and the mode of therapeutic effectiveness of psoralens used extensively in the photochemotherapy of psoriasis and vitiligo have been reviewed. Psoralen-induced skin photosensitization and the therapeutic action of psoralens involve two distinct types of reactions that occur independently of each other and concurrently when the psoralen-treated skin (oral or topical) is exposed to 320-400 nm UV radiation. The first, type I, occurs in the absence of oxygen (anoxic) reaction and primarily involves photoreactions with DNA; the second, type II, is a sensitized reaction dependent on oxygen and involves the formation of singlet oxygen (1O2), superoxide anion (O-.2), and hydroxy radicals. The photoreactive form of psoralen is its triplet state, and the sites of reaction are 1) the cell membrane of the epidermal, dermal, and endothelial cells; 2) the cytoplasmic constituents, such as enzymes, RNA, lysosomes, etc.; 3) the cell nuclei (DNA and chromatin); and 4) psoralen-sensitized production of 1O2, O-.2, and hydroxy radicals, which we believe are responsible for cell membrane damage and vasodilation. The major damage would be initiated by a type I reaction and would be seen in the form of nuclear damage to DNA resulting from the interaction of psoralen with DNA and to a lesser extent with RNA. The skin photosensitization response (erythema, edema, membrane damage, etc.) would result from a type II reaction involving the generation of 1O2. In vitro and in vivo metabolism of 4,5',8-trimethylpsoralen and 8-methoxypsoralen is briefly outlined.