Use of the yeast Saccharomyces cerevisiae as a pre-screening approach for assessment of chemical-induced phototoxicity.
Photoreactive chemicals can induce dermatological reactions when present in the skin exposed to sunlight. Thus, new chemicals absorbing above 290 nm should have their potential phototoxicity tested. In order to screen a large number of molecules with various physico-chemical properties, a microbiological method is helpful. To this end, the yeast Saccharomyces cerevisiae was evaluated for its ability to detect phototoxic compounds. Twelve products known to be phototoxic in vivo and previously used as standards for validating the regulatory test 3T3 NRU were used in this work. Eleven of them could be detected in the yeast assay and, among them, 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP), angelicin and, to a lower extend, tiaprofenic acid induced genetic alterations. Interestingly, a pre-incubation with yeast cells in the dark before exposure decreased the phototoxicity of 5-MOP and 8-MOP but had no effect on this of chlorpromazine and ketoprofen. Saccharomyces cerevisiae and Salmonella typhimurium (strains TA100 and TA102) were compared for the evaluation of 5-MOP and 8-MOP photogenotoxicity; only the yeast assay allowed to perform experiments in exposure conditions close to those encountered in environmental situations. Finally, an application of this experimental approach to the detection of traces of furocoumarins in fragrance materials was developed.
Marrot
L
L
L'OREAL Advanced Research, Life Sciences Research, Genotoxicity Group, 1 Avenue E Shueller, 93600 Aulnay-sous-Bois, France. lmarrot@rd.loreal.com
Labarussiat
A
A
Perez
P
P
Meunier
J R
JR
D000078223:5-Methoxypsoralen; D017484:Dermatitis, Phototoxic / Q000209:etiology*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008730:Methoxsalen / Q000031:analogs & derivatives / Q000633:toxicity; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000528:radiation effects; D012486:Salmonella typhimurium / Q000187:drug effects; D014466:Ultraviolet Rays
D000078223:5-Methoxypsoralen; D008730:Methoxsalen