Chronic low-dose radiation inhibits the cells death by cytotoxic high-dose radiation increasing the level of AKT and acinus proteins via NF-κB activation

Abstract

Purpose: This study explored the effects of low-dose and low-dose-rate irradiation in human lung fibroblast CCD-18Lu cells and examined the role of AKT (protein kinase B, PKB) in cellular responses.

Materials and methods: We examined cell survival after chronic low-dose irradiation (0.01 Gy or 0.05 Gy) with challenging high-dose (2 or 10 Gy) irradiation. We examined the effect of AKT activation on cell survival after chronic low-dose radiation using transduced cells with retroviral vector expressing constitutively active AKT (CA-AKT).

Results: Chronic low-dose priming irradiation increased cells viability against the challenging high-dose irradiation. Irradiation at 0.05 Gy increased cellular levels of AKT and acinus long form (L) and short form (S). The chronic low-dose radiation promoted cells proliferation in the exogenously expressed CA-AKT cells. It also increased nuclear factor-kappa B (NF-κB) activity in a biphasic induction pattern. Suppression of NF-κB activation by mutant form of inhibitor of kappa B alpha (IκBαM) antagonized the radiation-induced expression of AKT and acinus L and S.

Conclusions: Chronic low-dose radiation increases the levels of AKT and acinus proteins via NF-κB activation, and the NF-κB/AKT pathway responding to chronic low-dose irradiation plays an important role in the radiation adaptive response.

Keywords::

• AKT
• low-dose radiation
• adaptive response
• low-dose-rate
• NF-κB

Acknowledgements

The authors would like to thank Meeseon Jeong, PhD (Radiation Health Research Institute) for helpful contribution on statistical analysis of the data.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported by Grant 2010T100100303 from the Ministry of Knowledge Economy, Republic of Korea.