IONIZING-RADIATION INDUCES EXPRESSION AND BINDING-ACTIVITY OF THE NUCLEAR FACTOR-KAPPA-B

Recent studies have demonstrated that treatment of mammalian cells with ionizing radiation is associated with activation of gene expression. Although the signal transduction pathways stimulated by ionizing radiation remain unclear, our previous findings indicate that radiation induces specific genes at the transcriptional level. The present work has examined the effects of ionizing radiation on the transcription factor NF-kappa-B. The results demonstrate that ionizing radiation activates DNA binding of nuclear factor (NF)kappa-B. This effect was detectable at 2 grays (Gy) and reached a maximum at 5-20 Gy. At a dose of 20 Gy, the increase in NF-kappa-B binding activity was maximal at 2-4 h and then declined to pretreatment levels. The results also demonstrate that ionizing radiation transiently increases NF-kappa-B mRNA levels. However, the finding that induction of NF-kappa-B binding to DNA occurs in the presence of cycloheximide indicates that ionizing radiation activates preexisting NF-kappa-B protein. NF-kappa-B exists as a cytoplasmic protein before activation. Thus, our results suggest that ionizing radiation induces transduction pathways which include cytoplasmic signaling events.