Expression of a dominant negative I kappa B-alpha modulates hypersensitivity of ataxia telangiectasia fibroblasts to streptonigrin-induced apoptosis.

Ataxia telangiectasia (AT) cells exhibit greater levels of apoptosis than normal fibroblasts following exposure to X-rays or radiomimetic drugs. In this study, we investigated apoptosis in AT cells whose radiation sensitivity has been altered by transfection with a cDNA expressing truncated I kappa B-alpha (delta I kappa B-alpha). delta I kappa B-alpha functions as a dominant negative regulatory protein of NF-kappa B. The transfected cells (ATCL11) were compared to parental cells after treatment with the radiomimetic drug streptonigrin. ATCL11 cells exposed to streptonigrin demonstrated less apoptosis (approximately 2%) at 24 hr than did parental AT cells (approximately 24%). These data indicate that the mechanisms underlying apoptosis induction by streptonigrin are modulated by regulation of NF-kappa B.