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.