Radiation-induced expression of functional Fas ligand in EBV-positive human nasopharyngeal carcinoma cells

Ionizing radiation remains a major therapeutic tool against human cancers, especially epithelial tumors, which account for the majority of human malig nancies. Although pas and Fas-L are essential determinants of apoptosis, fe w data support their role in the cytotoxic effect of ionizing radiation. Ep stein-Barr-virus (EBV)-positive nasopharyngeal carcinoma (NPC) were chosen to address this question owing to their known sensitivity to ionizing radia tion and their constitutive expression of the Fas-receptor. We here report that, in xenografted NPC cells, Fas-L expression, which was very low in bas al conditions, was dramatically increased by tumor irradiation. Both the pa s receptor and the pas ligand were found to be functional in this model, an d a high proportion of irradiated NPC cells underwent apoptosis following t umor irradiation, Induction of Fas-L expression and apoptosis were observed for doses as low as 2 Cy, These data show an increase in Fas-L expression upon irradiation exposure, and strongly suggest that, in some epithelial ma lignancies, Fas-mediated apoptosis can play a major role in the anti-tumor effect of ionizing radiation, in the range of doses used for therapeutic ap plications. Int. J, Cancer 86:229-237, 2000, O 2000 Wiley-Liss,, Inc.