Fluoroquinolones as chemical tools to define a strategy for photogenotoxicity in vitro assessment

Today's lifestyle is often associated with frequent exposure to sunlight, b ut some xenobiotics used in drugs, cosmetics or food chemicals can produce adverse biological effects when irradiated. In particular, they can increas e the risk of photogenotoxicity already due to UV radiation itself. There i s thus a need to design appropriate approaches in order to obtain relevant data at the molecular and cellular level in this field. For ethical and pra ctical reasons, in vitro models can be very convenient at least for first e valuation tests. Here, we propose a strategy based on complementary experim ents to study the photogenotoxic potential of a compound. The fluoroquinolo nes BAYy3118 and lomefloxacin were used as standards to demonstrate the per formance of each test: photoinduced interaction with supercoiled circular D NA. photomutagenicity in the yeast Saccharomyces cerevisae, induction of DN A photodamage in cultured human skin cells as revealed by comet assay, and finally induction of specific phototoxic stress responses such as p53 activ ation or melanogenesis stimulation. Such a strategy should help to ensure t he safety of products likely to undergo environmental sunlight exposure. (C ) 2001 Elsevier Science Ltd. All rights reserved.