Background: Activation of the transcription factor NF-kappa B is part of th
e immediate early response of tissues to ionizing irradiation. This pathway
has been shown to protect cells from tumor necrosis factor-alpha, chemothe
rapy, and radiation therapy-induced apoptosis (programmed cell death). Howe
ver, because the role of NF-kappa B as a modifier of the intrinsic radiosen
sitivity of cancer cells is less clear, we have studied the impact of NF-ka
ppa B on the intrinsic radiosensitivity of human cancer cells. Methods: We
used PC3 prostate cancer cells and HD-MyZ Hodgkin's lymphoma cells transduc
ed with an adenovirus vector that contains a gene encoding a form of I kapp
a B (an inhibitor of NF-kappa B) that cannot be phosphorylated. This form o
f I kappa B v9ill remain bound to NF-kappa B; thus, NF-kappa B cannot be ac
tivated. We monitored NF-kappa B activity with a gel-shift assay and used a
colony-forming assay to assess clonogenicity and radiosensitivity, Results
: Constitutive DNA-binding: activity of NF-kappa B was dramatically decreas
ed in PC3 cells transduced with the I kappa B super-repressor gene. The clo
nogenicity of transduced PC3 cells declined to 19.6% of that observed for u
ntreated control cells, a finding similar to one we have previously demonst
rated for I kappa B-transduced HD-MyZ cells. However, inhibition of NF-kapp
a B activity in the surviving PC3 and HD-MyZ cells failed to alter their in
trinsic radiosensitivity, Conclusions: We conclude that activation of NF-ka
ppa B does not determine the intrinsic radiosensitivity of cancer cells, at
least for the cell lines tested in this study.