Cellular origin of ionizing radiation-induced NF-κB activation in vivo and role of NF-κB in ionizing radiation-induced lymphocyte apoptosis

Purpose: To investigate the cellular origin of ionizing radiation (IR)-induced NF-κB activation in vivo and the role of NF-κB in IR-induced lymphocyte apoptosis. Materials and methods: NF-κB activities were analysed by gel shift/ supershift assay in isolated murine T- and B-cells, macrophages (Mφ) and tissues from normal and T- and B-cell-deficient Rag1 mice with or without exposure to IR. IR-induced lymphocyte apoptosis was determined by analysis of 3,3′-dihexyloxacarbocyanine iodide (D _iOC₆) uptake, annexin-V staining and the sub-G0/1 population, or by TUNEL assay. Results: The results showed that IR activated NF-κB in lymphocytes, including both T- and B-cells, but failed to do so in Mφ. Furthermore, T- and B-cell-deficient Rag1 mice exposed to IR exhibited a significant reduction in NF-κB activation as compared with normal mice. Although NF-κB1 (p50) gene knockout or NF-κB decoy oligonucleotide treatment specifically inhibited IR-induced lymphocyte NF-κB activation, they had no significant effect on IR-induced lymphocyte apoptosis. Conclusions: This finding suggests that lymphocytes are the main cellular origin of IR-induced NF-κB activation in vivo. However, NF-κB activation has no significant effect on IR-induced lymphocyte apoptosis.