[Experimental 5-aminolevulinic acid-induced photodynamic therapy (ALA-PDT) of oral carcinomas. Procedures in treatment of solid tumors and elucidation of cell death].
OBJECTIVE
Of our own patients suffering from oral squamous cell carcinoma (OSCC), 96% possessed a 5-aminolevulinic acid (ALA)-induced tumor fluorescence. Consequently, the ALA-induced fluorescence of OSCC is suggested as an ideal tool for selective photodynamic therapy (PDT). The aim of the study was to demonstrate selective tumor damage and to analyze the cell death mode (apoptosis vs. necrosis) of OSCC cells in cell culture and in solid, deeply invasive xenotransplants in immunodeficient nude mice using intratumoral laser illumination.


METHODS
For ALA-PDT, laser light (635 nm, 0.75 W, 10 min, cooled application system) was used intratumorally as well as in cell culture. The therapeutic response was controlled by histology and immunohistochemistry (Ki-67 index). The apoptosis was evaluated by the TUNEL method and in vitro by flow cytometry. Mutations in the apoptosis-controlling p53 gene were investigated by direct genomic sequencing.


CONCLUSIONS
1. Although all OSCC exhibited an ALA-induced fluorescence in vivo, the evaluation of the cell lines showed differences in intensity of the ALA-induced fluorescence. This points to a different sensitivity of OSCC for ALA-PDT. 2. The use of a cooled laser light application system allowed intratumoral radiation and treatment of deeply invasive OSCC regions. 3. The cytotoxic effect of ALA-PDT in OSCC is evidenced by a diminution of proliferative activity and necrosis but not by apoptosis. 4. Functional mutations within the p53 gene were considered a possible reason for the absence of apoptosis induction by ALA-PDT.
Schleier
P
P
Klinik für Mund-, Kiefer- und Gesichtschirurgie, Friedrich-Schiller-Universität Jena. Peter.Schleier@med.uni-jena.de
Berndt
A
A
Berndt
A
A
Dahse
R
R
Zenk
W
W
Hyckel
P
P
Kosmehl
H
H
D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009062:Mouth Neoplasms / Q000473:pathology*; D009336:Necrosis; D009368:Neoplasm Transplantation; D010778:Photochemotherapy; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology
D000622:Aminolevulinic Acid