Genotype-dependent radiosensitivity: clonogenic survival, apoptosis and cell-cycle redistribution.

Purpose: We describe variations of three radiation-induced endpoints on the basis of cell genotype: Clonogenic survival, expression of apoptosis and cell-cycle redistribution.Methods: Clonogenic survival, apoptosis and cell-cycle redistribution are measured in multiple cell lines after exposure to radiation between 2 and 16 Gy. Cell lines varied in clonogenic radiosensitivity and expression of specific genes.Results: Clonal radiosensitivity is genotype-dependent, associating with four specific genes: A mutated form of Ataxia telangiectasia mutated (mutATM); with two forms of TP53, the gene that is template for tumor protein p53, wildtype TP53 (wtTP53) and mutated TP53 (mutTP53); and an unidentified gene in radioresistant glioblastoma cells. Apoptosis is also genotype-dependent showing elevated levels in cells that express mutATM and abrogated 14-3-3σ (an isoform of the 14-3-3 gene) but less variation for different forms of TP53. Cell-cycle redistribution varied in mutATM cells. Kinetics of apoptosis are b...