Ionizing radiation and the activation of caspase-8 in highly apoptosis-sensitive lymphoma cells

Purpose : Ionizing radiation induces apoptosis in human lymphoma cells. How ever, the participating molecules and their exact order is unknown. Caspase s are reported as essential cysteine proteases required for the activation and execution of programmed cell death. The activator caspase-8 is a key co mponent of the CD95/Fas/APO-1 death receptor-triggered apoptosis pathway. S ince contributing molecules for radiation-induced apoptosis and their exact order have not been analyzed in greater detail, the involvement of caspase -8 for radiation-induced apoptosis in human lymphoma cell lines was studied . Materials and methods: Apoptosis induction by CD95 stimulation and ionizing radiation was analyzed in eight different cell lines. In parallel, Western blotting tested activation of caspase-8. Results: Activation of caspase-8 by ionizing radiation occurred in five cel l lines and was associated with high apoptosis sensitivity. Caspase-8 activ ation and apoptosis was detectable in cells resistant to CD95 stimulation, so suggesting separate pathways for CD95 and radiation-induced caspase-8 ac tivation. Conclusion: The activator caspase-8 is activated during radiation-induced c ell death and, in some cases, ionizing radiation induces caspase-8 independ ently of the CD95 system.