title: Unirradiated cells rescue cells exposed to ionizing radiation: Activation of NF-κB pathway in irradiated cells.
abstract: We studied the involvement of NF-κB pathway activation in the rescue effect in HeLa and NIH/3T3 cells irradiated by α particles. Firstly, upon irradiation by 5 cGy of α particles, for both cell lines, the numbers of 53BP1 foci/cell at 12 h post-irradiation were significantly smaller when only 2.5% of the cell population was irradiated as compared to 100% irradiation, which demonstrated the rescue effect. Secondly, we studied the effect of NF-κB on the rescue effect through the use of the NF-κB activation inhibitor BAY-11-7082. Novel experimental setup and procedures were designed to prepare the medium (CM) which had conditioned the bystander cells previously partnered with irradiated cells, to ensure physical separation between rescue and bystander signals. BAY-11-7082 itself did not inflict DNA damages in the cells or have effects on activation of the NF-κB response pathway in the irradiated cells through direct irradiation. The rescue effect was induced in both cell lines by the CM, which was abrogated if BAY-11-7082 was added to the CM. Thirdly, we studied the effect of NF-κB on the rescue effect through staining for phosphorylated NF-κB (p-NF-κB) expression using the anti-NF-κB p65 (phospho S536) antibody. When the fraction of irradiated cells dropped from 100% to 2.5%, the p-NF-κB expression in the cell nuclei of irradiated NIH/3T3 cells increased significantly, while that in the cell nuclei of irradiated HeLa cells also increased although not significantly. Moreover, the p-NF-κB expression in the cell nuclei of irradiated HeLa cells and NIH/3T3 cells treated with CM also increased significantly.
authors.affiliation: Department of Physics and Materials Science, City University of Hong Kong, Hong Kong.
authors.forename: R K K
authors.initials: RK
authors.lastname: Lam
authors.affiliation: Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Physics and Materials Science, City University of Hong Kong, Hong Kong; State Key Laboratory in Marine Pollution, City University of Hong Kong, Hong Kong. Electronic address: peter.yu@cityu.edu.hk.
authors.forename: K N
authors.initials: KN
authors.lastname: Yu
mesh_terms: D000512:Alpha Particles; D000818:Animals; D024201:Bystander Effect / Q000528:radiation effects*; D018929:Cell Culture Techniques; D017077:Culture Media, Conditioned; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D041681:NIH 3T3 Cells; D009570:Nitriles / Q000494:pharmacology; D015398:Signal Transduction / Q000528:radiation effects*; D013450:Sulfones / Q000494:pharmacology; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D017077:Culture Media, Conditioned; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009570:Nitriles; D013450:Sulfones; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1
keywords: Alpha particles; Anti-NF-κB; BAY-11-7082; NF-κB; Radiation-induced bystander effect; Rescue effect