Role of nuclear factor-κB and P53 in radioadaptive response in Chang live cells

Understanding the mechanism governing radioadaptive response (RAR) has important implication for cancer risk assessment of a low-dose radiation (LDR). However the related knowledge especially the key gene of RAR is still limited. In this study, Chang liver cells were irradiated with a priming dose of 0.016 Gy, 0.08 Gy, or 0.16 Gy of γ-rays, and with 4 h interval, they were irradiated again with a challenging dose of 2 Gy or 3 Gy. It was found that only 0.08 Gy, but not 0.016 Gy or 0.16 Gy, induced RAR of micronuclei induction to the challenging irradiation. This RAR could be slightly reduced by pifithrin-α, an inhibitor of P53, however it was completely suppressed by BAY11-7082, an inhibitor of nuclear factor-κB (NF-κB). Further assays using western blotting and luciferase reporter gene found that nuclear NF-κB and its activity could be triggered by the priming irradiation of 0.08 Gy so that the expressions of them in the primed cells were higher than those in the cells exposed to the challenging dose alone. In contrast, LDR neither influenced the expressions of both P53 and phospho-P53 (ser15) nor enhanced P53 activity; the expression of phospho-P53 and the activity of P53 in the primed cells were lower than that in the non-primly challenged cells. Our results demonstrate that the induction of RAR relays on an optimum priming irradiation dose and it is NF-κB rather than P53 that contributes to RAR.