Cytotoxicity of Fas ligand against lymphoma cells with radiation-induced Fas antigen.
Fas antigen, also termed APO-1 or CD95, is a transmembrane protein and a member of the tumor necrosis factor receptor/nerve growth factor receptor superfamily which mediates apoptosis upon oligomerization. The Fas/Fas ligand system is considered to be a key regulator of apoptosis. Recently, we have demonstrated that Fas antigen expression is induced by low-dose irradiation of some types of lymphomas, and we also demonstrated that irradiation-induced Fas antigen expression increased with the passage of time until peaking at 48 h after irradiation in CML-C1, CML-C2, DL-40, and DL-95 cell lines. In this study, we also examined the potential cytotoxicity of Fas ligand peptide against several types of lymphoma/leukemia cell lines that showed induction of Fas antigen expression under irradiation. Flow cytometry analysis was performed at 6, 24 and 48 h after irradiation. Samples (1 x10(6) cells/ml) from irradiated and non-irradiated cells of each cell line were incubated with or without 5 microg/ml of Fas ligand peptide for 2 h at 37 degrees C in a humidified atmosphere of 5% carbon dioxide (CO2) in air. The killing effect of Fas ligand against cell lines of CML-C1, DL-40, and DL-95 were clearly identified as the percentage of cells with Fas antigen expression induced by irradiation. Concerning HD-70 cell line, for which soluble Fas antigen has been identified, the killing effects were clearly observed in samples pre-treated with PBS washings. To our knowledge, this is the first report describing a possible application of the Fas/Fas ligand system in treatment of certain types of malignancies in which Fas antigen is inducible by irradiation.
Ogawa
Y
Y
Department of Radiology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
Nishioka
A
A
Kubonishi
I
I
Inomata
T
T
Yoshida
S
S
Kataoka
S
S
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D053222:Fas Ligand Protein / Q000494:pharmacology*; D005720:Gamma Rays; D006689:Hodgkin Disease; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D016403:Lymphoma, Large B-Cell, Diffuse; D019014:fas Receptor / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D053222:Fas Ligand Protein; D019014:fas Receptor