Active and Higher Intracellular Uptake of 5-Aminolevulinic Acid in Tumors may be Inhibited by Glycine
| Autor: | S. A. Pahernik, Stefan Langer, Kai Rick, Rolf-Markus Szeimies, A. Botzlar, Christoph Abels, Alwin E. Goetz |
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| Rok vydání: | 1999 |
| Předmět: |
Male
Pathology medicine.medical_specialty Skin Neoplasms Glycine Protoporphyrins fluorescence kinetics Dermatology Deferoxamine Biochemistry chemistry.chemical_compound Cricetinae medicine Animals amelanotic melanoma topical application Amelanotic melanoma Molecular Biology Mesocricetus biology Protoporphyrin IX Biological Transport Melanoma Amelanotic Aminolevulinic Acid Cell Biology biology.organism_classification medicine.disease Fluorescence Molecular biology Spectrometry Fluorescence chemistry protoporphyrin Diffusion Chambers Culture Protoporphyrin Neoplasm Transplantation Intracellular Intravital microscopy Phenanthrolines |
| Zdroj: | Journal of Investigative Dermatology. 112(5):723-728 |
| ISSN: | 0022-202X |
| DOI: | 10.1046/j.1523-1747.1999.00579.x |
| Popis: | Topical 5-aminolevulinic acid is used for the fluorescence-based diagnosis and photodynamic treatment of superficial precancerous and cancerous lesions of the skin. Thus, we investigated the kinetics of 5-aminolevulinic acid-induced fluorescence and the mechanisms responsible for the selective formation of porphyrins in tumors in vivo. Using amelanotic melanomas (A-Mel-3) grown in dorsal skinfold chambers of Syrian golden hamsters fluorescence kinetics were measured up to 24 h after topical application of 5-aminolevulinic acid (1%, 3%, or 10%) for 1 h, 4 h, or 8 h by intravital microscopy (n = 54). Maximal fluorescence intensity in tumors after 1 h application (3% 5-aminolevulinic acid) occurred 150 min and after 4 h application (3% 5-aminolevulinic acid) directly thereafter. Increasing either concentration of 5-aminolevulinic acid or application time did not yield a higher fluorescence intensity. The selectivity of the fluorescence in tumors decreased with increasing application time. Fluorescence spectra indicated the formation of protoporphyrin IX (3% 5-aminolevulinic acid, 4 h; n = 3). The simultaneous application of 5-aminolevulinic acid (3%, 4 h) and glycine (20 microM or 200 microM; n = 10) reduced fluorescence in tumor and surrounding host tissue significantly. In contrast, neither decreasing iron concentration by desferrioxamine (1% and 3%; n = 10) nor inducing tetrapyrrole accumulation using 1, 10-phenanthroline (7.5 mM; n = 5) increased fluorescence in tumors. The saturation and faster increase of fluorescence in the tumor together with a reduction of fluorescence by the application of glycine suggests an active and higher intracellular uptake of 5-aminolevulinic acid in tumor as compared with the surrounding tissue. Shorter application (1 h) yields a better contrast between tumor and surrounding tissue for fluorescence diagnosis. The additional topical application of modifiers of the heme biosynthesis, desferrioxamine or 1,10-phenanthroline, however, is unlikely to enhance the efficacy of topical 5-aminolevulinic acid-photodynamic therapy at least in our model. |
| Databáze: | OpenAIRE |
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