Lack of involvement of ataxia telangiectasia mutated (ATM) in regulation of nuclear factor-kappa B (NF-kappa B) in human diploid fibroblasts

It has been suggested that the cellular response to exposure to ionizing ra diation involves activation of the transcription Factor nuclear factor-kapp a B (NF-kappa B) and that this response is defective in cells from individu als with ataxia telangiectasia (AT), In one study, it was found that SV40 l arge T-transformed cells derived from a patient null for the AT mutated (AT M) gene exhibited constitutive activation of NP-kappa B and that in those c ells, inhibition of NF-kappa B by expression of a modified form of I kappa B alpha led to correction of the radiosensitivity associated with the AT ph enotype [M, Jung ed at, Science (Washington DC), 268: 1691-1621, 1995]. Fro m those data, it was suggested that NF-kappa B played a role in the AT phen otype, We show here that normal diploid cells derived from AT patients do n ot exhibit constitutive activation of NF-kappa B, Furthermore, we provide d ata that the transformation process associated with SV40 large T antigen ex pression in AT-/- cells leads to aberrant cellular responses. Our studies h ighlight the importance of using diploid, nontransformed AT-/- cells for in vitro studies relevant to the AT phenotype whenever possible.