ATM (gene mutated in ataxia-telangiectasia) is a critical central component of the pleiotropic responses of cells to ionizing radiation-induced stress. To gain insight into molecular mechanisms and to enhance our understanding of ATM functions, we have advanced a human model cell system, derived from genetically defined immortal fibroblasts, and we have applied high-throughput genomic, proteomic and metabolomic technologies for a systems level analysis. The cellular characterizations reported here provide the background for application of a systems analysis to integrate transcription, post-translational modifications and metabolic activity induced by exposure of cells to ionizing radiation. We present here a summary of the derivation and characterization of cells comprising this model cell system and review applications of this model to systems analysis of ATM functions.