Photochemotherapy combines the use of a photosensitivity drug and long-wave UV-A light (320-400 nm). The topical application and oral administration of the selected psoralen, mostly 8-methoxypsoralen followed by UV-A irradiation (PUVA) have been proven to be very effective in the treatment of psoriasis, vitiligo, and cutaneous T-cell lymphoma.1 However, a statistically significant increase in the incidence of squamous cell carcinoma as well as malignant melanoma has been demonstrated in patients undergoing PUVA treatment.2,3 Skin cancers may arise as a result of the mutagenic psoralen photoadducts (and their mismatch or lack of repair) formed in keratinocytes during photochemotherapy. Other types of DNA damage may also contribute to the carcinogenicity of PUVA. Besides the direct interaction of psoralens with DNA, the role of reactive oxygen species (ROS) such as the superoxide anion (O2−), the hydroxyl radical (HO•), and singlet oxygen (1O2) in PUVA-induced cytotoxicity has been proposed.4 These ROS may cause oxidative damage to macromolecules such as DNA if not timely scavenged. Oxidative DNA damage has been known to be associated with gene mutations, carcinogenesis, and age-related disorders. 8-Hydroxy-2′-deoxyguanosine (8-OHdG), a widely used biomarker of oxidative DNA damage, has been implicated in several carcinogenic processes, including skin cancer, and is used as an indicator of overall oxidative DNA damage in vivo.
Goldstein AE, Lebwohl M, Wei H. Comparison of Urinary 8-Hydroxy-2′-deoxyguanosine in Patients Treated With Topical Corticosteroids, UV-B, and Psoralen UV-A Therapies. Arch Dermatol. 2000;136(6):808-810. doi: