Photogenotoxicity of mammalian cells: a review of the different assays for in vitro testing.
During the past several years, phototoxicity has been studied at the molecular level, and these studies have provided new insights in the field of DNA lesion characterization, DNA repair and cell response to ultraviolet (UV)-induced stress. The development of new antibiotics and antiinflammatory drugs has highlighted the necessity to develop the assessment of phototoxicity in the safety evaluation of new chemical compounds. This paper aims at reviewing the known molecular mechanisms of the cellular response to UV-induced stress, the in vitro methods that can be proposed and used to screen for toxicity of sunlight and the photosensitization process resulting from the activation of drugs by light. UV sources, biological systems and endpoints of interest in that particular objective are listed. Phototoxic effects span from the cytotoxic-apoptotic effect to the induction of primary DNA damage, DNA repair and a variety of stress genes acting on the cell cycle and the fate of the cell. Ultimately, it can lead to the induction of hereditary DNA modification. A variety of assays are proposed to specifically address all these particular consequences of UV-induced toxicity.
Meunier
Jean-Roch
JR
L'Oréal Advanced Research, Life Sciences Research, Aulnay-sous-Bois, France. jrmeunier@recherche.loreal.com
Sarasin
Alain
A
Marrot
Laurent
L
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects*; D006801:Humans; D008027:Light; D014466:Ultraviolet Rays