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

Photochemotherapy with 8-methoxypsoralen and long wavelength ultraviolet ra diation (PUVA) is commonly used to treat psoriasis and vitiligo, These vast ly different diseases respond to the therapy by different mechanisms even t hough the immediate effects of the therapy photoadduct formation - is the s ame for both. Because psoriasis is not cured by PUVA, patients receive many treatments over their lifetime and develop a significant risk for the deve lopment of skin cancers (primarily squamous cell carcinomas). In this revie w the basic aspects of psoralen photobiology are reviewed briefly. In addit ion the impact of the analysis of mutations in the tumor suppressor gene, p 53, are summarized. An unexpected mutation spectrum (very few T --> A trans versions and frequent UVB signature C --> T transitions) suggest that effec ts 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 im prove the therapeutic efficacy of PUVA by a careful evaluation of the mode of delivery.