Psoriasis, PUVA, and skin cancer--molecular epidemiology: the curious question of T-->A transversions

Photochemotherapy with 8-methoxypsoralen and long wavelength ultraviolet radiation (PUVA) is commonly used to treat psoriasis and vitiligo. These vastly different diseases respond to the therapy by different mechanisms even though the immediate effects of the therapy - photoadduct formation - is the same for both. Because psoriasis is not cured by PUVA, patients receive many treatments over their lifetime and develop a significant risk for the development of skin cancers (primarily squamous cell carcinomas). In this review the basic aspects of psoralen photobiology are reviewed briefly. In addition the impact of the analysis of mutations in the tumor suppressor gene, p53, are summarized. An unexpected mutation spectrum (very few T-->A transversions and frequent UVB signature C-->T transitions) suggest that effects other than direct DNA photoadduct formation may be at play. The roles of reactive oxygen species-induced base changes as well as other clastogenic factors are discussed. This analysis suggests that it may be possible to improve the therapeutic efficacy of PUVA by a careful evaluation of the mode of delivery.