PSORALEN PHOTOCHEMOTHERAPY, CLINICAL EFFICACY, AND PHOTOMUTAGENICITY - THE ROLE OF MOLECULAR EPIDEMIOLOGY IN MINIMIZING RISKS

Photochemotherapy employing 8-methoxypsoralen and ultraviolet radiatio n (PUVA) is widely used in the treatment of psoriasis. The photoactiva tion of psoralens in skin cells leads to DNA photoadduct formation whi ch may be responsible for the efficacy of PUVA. Subsequent mutations m ay lead to the increased incidence of squamous cell carcinoma (SCC). M utations in the p53 tumor suppressor gene have been detected in many h uman cancers. In this review, p53 mutation spectra in murine and human SCC are compared to those obtained From murine cells and skin treated with PUVA as well as to the p53 mutation spectrum in human solar SCC. While the expected psoralen-type mutations at alternating AT sites we re detected in the treated cells and murine SCC (average Frequency > 4 0%), such mutations were not commonly detected in the human SCC (<10%) . Other common mutations in the human SCC included: CG --> TA transiti ons (18%) and CG --> AT and TA --> GC transversions (17 and 25%, respe ctively). In addition, the frequency of UVB-type mutations at dipyrimi dine sites (CC --> TT) in the SCC PUVA-treated psoriasis patients was comparable to that in patients with SCC from only solar exposure. A re view of therapeutic history of these patients showed that many had als o received UVB phototherapy. Furthermore, because sunlight is thought to be beneficial for psoriasis, nontherapeutic, casual UVB exposure ca nnot be excluded. Thus, the PUVA SCC may have arisen from the solar mu tations and PUVA may enhance tumor progression by other epigenetic eff ects. (C) 1998 Wiley-Liss, Inc.