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In a population of cells undergoing oxidative stress, an individual cell either succumbs to apoptotic cell death or maintains homeostasis and survives. Exposure of PC-12-D₂R cells to 200 μm hydrogen peroxide (H₂O₂) induces apoptosis in about half of cells after 24 h. After 1-h exposure to 200 μm H₂O₂, both antiapoptotic extracellular regulated kinase (ERK) phosphorylation and pro-apoptotic Ser-15-p53 phosphorylation are observed. Microarray and real-time PCR assays of gene expression after H₂O₂ exposure identified several transcripts, including egr1, that are rapidly induced downstream of ERK. Single cell analysis of egr1 induction and of phospho-ERK and phospho-p53 formation revealed the presence of two distinct cellular programs. Whereas the proportion of cells activating ERK versus p53 at 1 h depended on H₂O₂ concentration, individual cells showed exclusively either phospho-p53 formation or …