In Vivo Detection of Ultraviolet Photoproducts and Their Repair in Purkinje Cells

We previously developed a highly sensitive method to assess in situ repair kinetics of ultraviolet (UV)-induced DNA photoproducts in epidermal cells using monoclonal antibodies specific for cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts (64PPs) by immunohistochemistry. In order to determine whether nucleotide excision repair capacity is operative in postmitotic mature neurons, brain surfaces of adult mice were exposed to UVB, and induction and removal of CPDs and 64PPs in Purkinje cell DNA were assessed immunohistochemically. UVB penetrated brain tissue to a depth sufficient to allow quantitative study. CPDs but not 64PPs were clearly detectable in the nuclei of Purkinje cells at doses >500 J/m 2 , in a dose-dependent manner. A time course experiment showed a statistically significant decrease of CPDs with time after irradiation. Although there was no apparent removal on Day 1, about half of CPDs were removed within 5 days, and the repair was essentially completed by Day 10. We conclude that non-dividing cerebellar neuronal cells can indeed repair UV-induced DNA damage, but with relatively low efficiency as compared with dividing epidermal cells.