Identification of a non-dividing subpopulation of mouse and human epidermal cells exhibiting high levels of persistent ultraviolet photodamage

The distribution and persistence of cyclobutane pyrimidine dimers were inve stigated in mouse skin after chronic and acute exposures to ultraviolet-B r adiation. We found that DNA damage accumulated in response to chronic irrad iation and persisted in a unique set of epidermal cells located at the basa l layer. Treatment with a tumor promoter caused the heavily damaged epiderm al cells to divide and p53-immunopositive clusters to form within 24 h sugg esting that these cells may be progenitors of the mutant p53 clusters assoc iated with actinic keratoses and squamous cell carcinomas. In contrast to l ow fluence chronic irradiation, daily treatment with a higher fluence of ul traviolet-B produced extensive hyperplasia and considerably reduced penetra tion of photodamage. Exposure of chronically irradiated skin to an acute "s unburn dose" of ultraviolet-B also produced significant epidermal hyperplas ia and resulted in complete loss of heavily damaged basal cells within 4 d postirradiation. The occurrence and distribution of cyclobutane dimers in h uman skin correlated well with putative sunlight exposure and resembled tha t observed in ultraviolet-B-irradiated mice. Heavily damaged basal cells we re observed at various sites, including those receiving sporadic sunlight e xposure, suggesting that these cells may play an important role in carcinom a formation in humans.