Induction, repair and accumulation of thymine dimers in the skin of UV-B-irradiated hairless mice

A monoclonal antibody specific for cyclobutane thymine dimers in DNA was used in immunofluorescence studies to detect these lesions in skin sections taken from hairless mice that had been irradiated with UV-B. The dimer-specific fluorescence in epidermal cell nuclei was quantified with fluorescence microscopy through computer-mediated image processing and analysis. After a UV-dose of 500 J/m2, thymine dimers could easily be detected. Rapid removal of these lesions in vivo was observed during the first 4 h after exposure, but at 24 h ∼40% of the dimers still persisted. Thymine dimers accumulated in the skin of mice subjected chronically to a dose regimen of 1000 J/m2 UV-B per day. In the first week strong accumulation of dimers was observed. At day 3 to 4 it reached a maximum, after which a decrease to a more constant level occurred. Concomitant with this decrease the number of epidermal cell layers increased after the first week. After 3 months of irradiation, mice started to develop skin tumours. At that time point the epidermis had thickened to contain up to 10 cell layers, compared to 1-2 layers in unirradiated mice, but thymine dimers were still induced. (author)