Abstract
Ionizing radiation shares with proinflammatory cytokines a pathway that involves reactive oxygen species and activation of the redox-sensitive nuclear transcription factor NF-κB, which leads to expression of inflammatory and cell survival programs. NF-κB activation normally requires phosphorylation of its inhibitor IκB and the inhibitor's subsequent degradation by the proteasome. Nonlinear dose-response curves have been reported for both radiation-induced cytokines and NF-κB and IκB expression with maximum exposures of less than 2 Gy and greater than 4 Gy, respectively. Radiation-inhibited proteasomes function over a wide dose range, suggesting that the proteasome is a redox-sensitive target for radiation that may function along with transcription to cause nonlinear dose-response relationships for early expression of many molecules, including NF-κB and cytokines. These pathways are relevant to low-dose radiation effects, adaptive responses, and carcinogenesis.