Marrot L, Belaidi J P, Chaubo C, Meunier J R, Perez P, Agapakis-Causse C
L'OREAL Advanced Research, Life Sciences Research, Investigative Toxicology Department, Aulnay-sous-bois, France.
Toxicol In Vitro. 2001 Apr;15(2):131-42. doi: 10.1016/s0887-2333(01)00004-2.
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.
如今的生活方式常常与频繁接触阳光相关，但药物、化妆品或食品化学制品中使用的某些外源性物质在受到光照时会产生不良生物学效应。特别是，它们已经会因紫外线辐射本身而增加光遗传毒性的风险。因此，有必要设计适当的方法，以便在该领域的分子和细胞水平上获得相关数据。出于伦理和实际原因，体外模型至少对于初步评估测试可能非常方便。在此，我们提出一种基于互补实验的策略，以研究化合物的光遗传毒性潜力。氟喹诺酮类药物BAYy3118和洛美沙星用作标准品，以证明每项测试的性能：与超螺旋环状DNA的光诱导相互作用、在酿酒酵母中的光致突变性、彗星试验显示的在培养的人皮肤细胞中DNA光损伤的诱导，以及最后诱导特定的光毒性应激反应，如p53激活或黑素生成刺激。这样一种策略应有助于确保可能遭受环境阳光照射的产品的安全性。
