Induced apoptosis of motor neurons is associated with accumulation of mitochondria, peroxynitrite formation and hydroxyl radical damage to DNA (116) and p53 accumulation (117). We have used single-cell gel electrophoresis (comet assay) to detect DNA-SSB in motor neurons (118). Exposure of motor neurons to NO donors, H202, and NO donor plus H202 induces rapidly DNA-SSB and causes motor neuron degeneration. Peroxynitrite causes DNA-SSB in motor neurons. DNA-SSB accumulate slowly in injured motor neurons prior to apoptosis and the comet fingerprint is similar to NO toxicity. Thus, motor neurons challenged by oxidative stress and axotomy accumulate DNA-SSB early in their degeneration. The formation of peroxynitrite appears to be involved in the mechanisms of DNA damage upstream to p53 mediated apoptosis of motor neurons.