Activation of the Nuclear Factor κB pathway by heavy ion beams of different linear energy transfer

Abstract

Purpose: Risk assessment of radiation exposure during long-term space missions requires the knowledge of the relative biological effectiveness (RBE) of space radiation components. Few data on gene transcription activation by different heavy ions are available, suggesting a dependence on linear energy transfer. The transcription factor Nuclear Factor κB (NF-κB) can be involved in cancerogenesis. Therefore, NF-κB activation by accelerated heavy ions of different linear energy transfer (LET) was correlated to survival.

Materials and methods: NF-κB-dependent gene induction after exposure to heavy ions was detected in stably transfected human embryonic kidney 293 cells (HEK-pNF-κB-d2EGFP/Neo cells carrying a neomycin resistance), using the destabilized Enhanced Green Fluorescent Protein (d2EGFP) as reporter.

Results: Argon (LET 272 keV/μm) and neon ions (LET 91 keV/μm) had the highest potential to activate NF-κB, resulting in a RBE of 8.9 in comparison to 150 kV X-rays. The RBE for survival also reached its maximum in this LET range, with a maximal value of 2.

Conclusions: NF-κB might be involved in modulating survival responses of cells hit by heavy ions in the LET range of 91–272 keV/μm and could therefore become a factor to be considered for risk assessment of radiation exposure during space travel.

Keywords::

• Nuclear Factor κB
• linear energy transfer
• heavy ion
• space mission
• relative biological effectiveness

Acknowledgements

We thank Dr Hermann Rothard and all the physicists of CIMAP (Caen, France) involved in dosimetry and the beam operator team at GANIL for providing us valuable advice and many help given during numerous night shifts at the French Heavy Ion Accelerator GANIL. The travel costs to the GANIL were supported in part by the European Union (EURONS). Luis Spitta, Melanie Thelen, Dimitri Ott, Britta Langen, Rebecca Ruland, Kristina Koch, Yueyuan Hu, Arif Ali Chishti and Sebastian Feles are acknowledged for their valuable help during beam times at GANIL.

Declaration of interest

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

Notice of correction:

This paper published online on 6 July 2011 contained an error. Figure 1 A was published twice instead of Figure 1B. This current version of the paper is the correct version. The publisher would like to apologize for the inconvenience caused.