Induction of nuclear factor κB after low-dose ionizing radiation involves a reactive oxygen intermediate signaling pathway

Reactive oxygen intermediates (ROIs) have been found to be the messengers in the activation of the κB transcription regulator in mitogen- or cytokine- stimulated cells, operating in conjunction with or independently of various other mechanisms; these include Ca⁺⁺-dependent and PKC-dependent cytoplasmic signaling pathways. We have recently reported that low-dose ionizing radiation induces NF-κB in human lymphoblastoid 244B cells. Since ionizing radiation generates free radicals in cells, we have investigated whether the ROIs generated by ionizing radiation induce NF-κB 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-dose ionizing radiation (0.1-2.0 Gy) activates κB transcription factor transiently with a maximal induction at 0.5 Gy exposure, but also demonstrate mechanistically that the activation of NF-κB 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 activation process is mediated by ROIs. These findings support the idea that ROIs can regulate the κB elements which in turn can serve as response elements for oxidant stress.