Fluoroquinolones as chemical tools to define a strategy for photogenotoxicity in vitro assessment.
Today's lifestyle is often associated with frequent exposure to sunlight, but some xenobiotics used in drugs, cosmetics or food chemicals can produce adverse biological effects when irradiated. In particular, they can increase the risk of photogenotoxicity already due to UV radiation itself. There is 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 practical reasons, in vitro models can be very convenient at least for first evaluation tests. Here, we propose a strategy based on complementary experiments to study the photogenotoxic potential of a compound. The fluoroquinolones BAYy3118 and lomefloxacin were used as standards to demonstrate the performance of each test: photoinduced interaction with supercoiled circular DNA, photomutagenicity in the yeast Saccharomyces cerevisae, induction of DNA photodamage in cultured human skin cells as revealed by comet assay, and finally induction of specific phototoxic stress responses such as p53 activation or melanogenesis stimulation. Such a strategy should help to ensure the safety of products likely to undergo environmental sunlight exposure.
Marrot
L
L
L'OREAL Advanced Research, Life Sciences Research, Investigative Toxicology Department, Aulnay-sous-bois, France. lmarrot@recherche.loreal.com
Belaidi
J P
JP
Chaubo
C
C
Meunier
J R
JR
Perez
P
P
Agapakis-Causse
C
C
D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects*; D004278:DNA, Superhelical / Q000528:radiation effects*; D024841:Fluoroquinolones; D006801:Humans; D066298:In Vitro Techniques; D008544:Melanocytes / Q000528:radiation effects; D014442:Monophenol Monooxygenase / Q000528:radiation effects; D009152:Mutagenicity Tests / Q000379:methods*; D010777:Photochemistry; D010858:Pigmentation / Q000528:radiation effects; D015363:Quinolones / Q000494:pharmacology* / Q000633:toxicity; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012867:Skin / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000890:Anti-Infective Agents; D004278:DNA, Superhelical; D024841:Fluoroquinolones; D015363:Quinolones; D016159:Tumor Suppressor Protein p53; C079807:Bay Y3118; D014442:Monophenol Monooxygenase; C053091:lomefloxacin