Sun, Drugs, and Skin Cancer:  A Continuing Saga

Photocarcinogenesis continues to be an active field of investigation for dermatologists and photobiologists because of the continuing increased incidence of nonmelanoma skin cancers and of early cutaneous melanomas. Epidemiological and molecular studies provide supporting evidence that solar radiation is a major carcinogen for nonmelanoma skin cancers and melanomas. The wavelengths of UV radiation that reach the surface of the Earth and are able to penetrate skin consist of UV-B (280-315 nm) and UV-A (315-400 nm). Most of the UV radiation that reaches the Earth is UV-A. Only 5% to 10% is in the UV-B range. The major focus of investigations has been UV-B because it is thought to be the more carcinogenic wavelength by virtue of its ability to be directly absorbed by cellular DNA, directly causing damaging mutations in multiple tumor suppressor genes as well as diminishing the skin's immune responses. Mutations induced by UV-B are characterized by the presence of C → T or CC → TT patterns (cyclobutane pyrimidine dimers) and pyrimidine-pyrimidone 6-4 photoproducts (6-4 PP). These are quite specific to damage caused by UV and are referred to as “UV-signature mutations.” ¹