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The Relevance of Photomutagenicity Testing as a Predictor of Photocarcinogenicity

Federal Institute for Drugs and Medical Devices, Berlin, Germany

Peter Kasper

Federal Institute for Drugs and Medical Devices, Berlin, Germany

Today's lifestyle is associated with frequent and intense exposure to ultraviolet radiation (UVR). The tumorigenic effects of 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 photody-namic generation of active oxygen species involving endogenous or exogenous photosen sitizers. Several pharmaceuticals are known to act as photosensitizers. Photoinstable phenothiazines, furocoumarins, and fluoroquinolones were shown to be very efficient inducers of chromosomal damage in mammalian cells in culture. Photocar cinogenicity testing in hairless mice of furocoumarins and several fluoroquinolones demonstrated a higher incidence and a shorter latent period for skin tumors compared to UVR alone. These data show a good correlation between the photomutagenic and photocarcinogenic potential of these compounds. Although mammalian cells possess effective repair mechanisms for oxidative damage, photoproducts, and dimers, these repair mechanisms can be overloaded. Eventually, unrepaired damage leads to gene mutations or chromosomal damage in exposed cells and to tumors in the skin. Therefore, in vitro photomutageni-city testing in mammalian cells may be an early and easy-to-measure predictor of the photocarcinogenic potential of a pharmaceutical.

Key Words: photomutagenicity • photocarcinogenic testing • fluoroquinolones • UV

International Journal of Toxicology, Vol. 17, No. 5, 551-558 (1998)
DOI: 10.1080/109158198226053


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