INDUCTION OF NUCLEAR FACTOR KAPPA-B AFTER LOW-DOSE IONIZING-RADIATIONINVOLVES A REACTIVE OXYGEN INTERMEDIATE SIGNALING PATHWAY

Reactive oxygen intermediates (ROIs) have been found to be the messeng ers in the activation of the kappa B transcription regulator in mitoge n- or cytokine-stimulated cells, operating in conjunction with or inde pendently of various other mechanisms; these include Ca++-dependent an d PKC-dependent cytoplasmic signaling pathways, We have recently repor ted that low-dose ionizing radiation induces NF-kappa B in human lymph oblastoid 244B cells. Since ionizing radiation generates free radicals in cells, we have investigated whether the ROIs generated by ionizing radiation induce NF-kappa B activity, and also whether they do so by a similar mechanism as in cells treated with PMA or H2O2. The results not only confirm a previous observation from our laboratory that low-d ose ionizing radiation (0.1-2.0 Gy) activates kappa B transcription fa ctor transiently with a maximal induction at 0.5 Gy exposure, but also demonstrate mechanistically that the activation of NF-KB by low-dose ionizing radiation can be inhibited considerably by the antioxidant N- acetyl-L-cysteine, indicating that at least the major part of the acti vation process is mediated by ROIs. These findings support the idea th at ROIs can regulate the kappa B elements which in turn can serve as r esponse elements for oxidant stress.