Development of a test system for mutagenicity of photosensitizers using Drosophila melanogaster.
In the past few years, there has been an increase in the application of photosensitizers for medical purposes. A good standardized test system for the evaluation of the mutagenic potentials of photosensitizers is therefore an indispensable device. In the standard Ames test, white light itself was proven to be mutagenic and the result influenced by the light source. Lack of a reliable positive control is another problem in many genotoxicity test systems used for the evaluation of mutagenicity of photosensitizers. Based on the validated somatic mutation and recombination test, known as SMART, and using Drosophila melanogaster, we developed the Photo-SMART and demonstrated that methylene blue, known to induce photomutagenicity, can act as a positive control in the presented test system. The SMART scores for the loss of heterozygosity caused predominantly by homologous mitotic recombination. The Photo-SMART can be used to detect photogenotoxicity caused by short-lived photoproducts or by stable photoproducts or both. We demonstrated the Photo-SMART to be a good standardized test system for the evaluation of mutagenic potentials of the photosensitizer 5,10,15-tris(4-methylpyridinium)-20-phenyl-[21H,23H]-porphine trichloride (TPP). We demonstrated that TPP was mutagenic using the Photo-SMART. For hematoporphyrin, the results of the Photo-SMART indicate the absence of mutagenicity.
Smijs
Threes G M
TG
Leiden University Medical Centre, Sylvius Laboratory, Wassenaarseweg 72, 2333 AL, Leiden, The Netherlands. g.m.t.smijs@lumc.nl
Nivard
Madeleine J M
MJ
Schuitmaker
Hans J
HJ
D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics; D005123:Eye / Q000187:drug effects / Q000378:metabolism; D006415:Hematoporphyrins / Q000633:toxicity; D008027:Light; D008751:Methylene Blue / Q000633:toxicity; D008938:Mitosis; D009152:Mutagenicity Tests / Q000379:methods*; D017319:Photosensitizing Agents / Q000633:toxicity*; D011166:Porphyrins / Q000633:toxicity*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D013223:Statistics as Topic; D016019:Survival Analysis
D029721:Drosophila Proteins; D006415:Hematoporphyrins; D017319:Photosensitizing Agents; D011166:Porphyrins; C107018:porphine; D011494:Protein Kinases; C093503:wts protein, Drosophila; D008751:Methylene Blue