gamma-radiation-induced growth arrest and apoptosis in p53-null lymphoma cells is accompanied by modest transcriptional changes in many genes

Damage to DNA produces cell cycle arrest, apoptosis, or both. The response in cells with p53 tumor suppressor function involves transcriptional change s, but whether that holds for cells lacking active p53, as in most tumors, is not known. Better characterization of the DNA damage response in tumors lacking p53 function is relevant to cytotoxic therapy. We have explored whe ther gamma-irradiated p53-null mouse T lymphoma cells undergo marked change s in transcription. Their arrest in G(2)/M prior to apoptosis required tran scription. Transcripts whose abundance altered on irradiation mere sought b y subtractive hybridization, and 1010 candidate clones from two oppositely enriched cDNA populations mere sequenced. Hybridization revealed small (<3- fold) increases or decreases in the transcripts of more than 15 genes, incl uding some implicated in cell cycle control (e.g., BTG, Bap1) or apoptosis (e.g., STAT1, calpain), but no marked changes like those associated with ot her forms of T-cell death. Moreover, the expression of some critical apopto sis regulators, such as Bcl-2 family members, did not change. Hence, the G( 2)/M arrest and apoptosis in the irradiated p53-null lymphoma appears to in volve modest expression changes for many genes, but post-transcriptional al terations may be more critical.