Photoaddition by Furocoumarins

Abstract

In photobiology, the photoreactions involving the formation of C₄-cyclobutane type adducts in DNA, such as the formation of pyrimidine dimers (Setlow and Carrier, 1966) by short wave UV radiation and the photoaddition of furocoumarins to pyrimidines in DNA (Musajo and Rodighiero, 1972; Hearst et al., 1984), have been of particular importance because of the relatively high chemical stability of these lesions during biochemical analysis. Pyrimidine dimers have been important model lesions (see for review Kim and Sancar, 1993; Sancar and Tang, 1993; Hoeijmakers, 1993a, b), not only for elucidating major DNA repair mechanisms, but also for investigating the mechanisms of photoinduced mutagenesis and carcinogenesis. Likewise, photoadditions induced by furocoumarins have been useful for elucidating the structure and function of chromatin (Cimino et al., 1985) as well as for studying the repair and genotoxic consequences of well defined bulky photolesions in DNA (see for review Averbeck, 1989). These studies are especially interesting because of the wide use of furocoumarins in photomedicine (see for review Averbeck, 1989). The so-called psoralen plus UVA, PUVA-therapy, has been found very beneficial in the treatment of psoriasis (Parrish et al., 1974, 1982), the T-cell lymphoma mycosis fungoides (Gilchrest et al., 1976) and other skin diseases, such as atopic dermatitis (Jeckler, 1992), lichen planus (Ortonne et al., 1978), graft versus host disease (Hymes et al., 1985; Kapoor et al., 1992), pruritus of human immunodeficiency virus infection and acquired immunodeficiency syndrome (Gorin et al., 1989). Furthermore, the recently developed photopheresis therapy, i. e. extracorporeal irradiation of 8-methoxypsoralen containing blood, has been shown useful in the treatment of cutaneous T-cell lymphoma and other T-cell mediated diseases, such as pemphigus vulgaris, lupus erythematosus, psoriatic arthropathy, myasthenia gravis and chronic lymphocytic leukemia and AIDS related complex (Edelson et al., 1987, 1991) and has been tested in an animal model (Van Iperen and Beijersbergen van Henegouwen, 1993). To what extent furocoumarin-plus-UVA induced photoadditions to DNA are involved in the photochemotherapeutic effects is still a matter of debate.