Photochemical genotoxicity and photochemical carcinogenesis--two sides of a coin?

The direct tumorigenic effects of ultraviolet radiation (UVR) are well known. Specifically, the premutagenic lesions of UVB (290-320 nm), are known to be the most important molecular events in UVR tumorigenicity. The less carcinogenic UVA (320-400 nm) mainly generates oxidative damage in the DNA via photodynamic generation of active oxygen species involving endogenous or exogenous photosensitizers. Several pharmaceuticals are known to act as photosensitizers. Photoinstable phenothiazines, furocoumarins and fluoroquinolones were shown to be very efficient inducers of chromosomal damage in UV-irradiated mammalian cells. Testing for photochemical carcinogenesis in hairless mice of furocoumarins and several fluoroquinolones resulted in a higher incidence and a shorter latent period for skin tumors compared to UVR alone. Overall, the correlation of experimental data between photochemical carcinogens and photochemical genotoxins is quite convincing. Therefore, testing for photochemical genotoxicity preferably in mammalian cells in vitro may be an easy hazard identification approach for photochemical carcinogens. However, further factors such as immunosuppression, irritation and dedifferentiation are to be considered for risk assessment in photochemical carcinogenesis.