Carbon-Ion-Induced Activation of the NF-κB Pathway

Hellweg, C. E., Baumstark-Khan, C., Schmitz, C., Lau, P., Meier, M. M., Testard, I., Berger, T. and Reitz, G. Carbon-Ion-Induced Activation of the NF-kappa B Pathway. Radiat. Res. 175, 424-431 (2011). Carbon-ion cancer therapy offers several physical and radiobiological advantages over conventional photon cancer therapy. The molecular mechanisms that determine cellular outcome, including the activation of transcription factors and the alteration of gene expression profiles, after carbon-ion exposure are still under investigation. We have previously shown that argon ions (LET 272 keV/mu m) had a much higher potential to activate the transcription factor nuclear factor kappa B (NF-kappa B) than X rays. NF-kappa B is involved in the regulation of cellular survival, mostly by antiapoptosis and cell cycle-regulating target genes, which are important in the resistance of cancer cells to radiotherapy. Therefore, activation of the NF-kappa B pathway by accelerated carbon ions (LET 33 and 73 keV/mu m) was examined. For comparison, cells were exposed to 150 kV X rays and to accelerated carbon ions. NF-kappa B-dependent gene induction after exposure was detected in stably transfected human 293 reporter cells. Carbon ions and X rays had a comparable potential to activate NF-kappa B in human cells, indicating a comparable usefulness of pharmacological NF-kappa B inhibition during photon and carbon-ion radiotherapy. (C) 2011 by Radiation Research Society