Oxidative nucleotide damage and superoxide dismutase expression in the brains of xeroderma pigmentosum group A and Cockayne syndrome.

Xeroderma pigmentosum group A (XPA) and Cockayne syndrome (CS) are caused by a genetic defect of nucleotide excision repair mechanisms, showing cutaneous hypersensitivity to sunlight and progressive neurological disturbances. The cause of neurological abnormalities has yet to be clarified and fundamental treatments have never been established in both disorders. In order to investigate neurodegeneration of XPA and CS, we immunohistochemically examined deposition of oxidative stress-related materials of nucleotides and expression of two types of superoxide dismutase (SOD) in the brains from autopsy cases of XPA and CS. Cases of XPA but not CS demonstrated nuclear deposition of 8-hydroxy-2'-deoxyguanosine and cytoplasmic deposition of 8-hydroxyguanosine, being speculated as oxidative stress-related materials of DNA and RNA, respectively, in the globus pallidus. Four of five XPA cases exhibited reduced neuronal immunoreactivity for Cu/ZnSOD in the cerebral and cerebellar corteces in addition to the basal ganglia, and two XPA cases showed reduced immunoreactivity for MnSOD in the brain regions examined. In contrast, five CS cases demonstrated comparatively preserved immunoreactivity for Cu/ZnSOD and MnSOD. Both XPA and CS cases showed increased cytoplasmic immunoreactivity for Cu/ZnSOD and/or MnSOD in the microglial cells in the cerebral and cerebellar white matters. These findings suggest that oxidative damage to nucleotides and disturbed SOD expression can be involved in neurodegeneration in XPA but not CS.