title: Identification of a non-dividing subpopulation of mouse and human epidermal cells exhibiting high levels of persistent ultraviolet photodamage.
abstract: The distribution and persistence of cyclobutane pyrimidine dimers were investigated in mouse skin after chronic and acute exposures to ultraviolet-B radiation. We found that DNA damage accumulated in response to chronic irradiation and persisted in a unique set of epidermal cells located at the basal layer. Treatment with a tumor promoter caused the heavily damaged epidermal cells to divide and p53-immunopositive clusters to form within 24 h suggesting that these cells may be progenitors of the mutant p53 clusters associated with actinic keratoses and squamous cell carcinomas. In contrast to low fluence chronic irradiation, daily treatment with a higher fluence of ultraviolet-B produced extensive hyperplasia and considerably reduced penetration of photodamage. Exposure of chronically irradiated skin to an acute "sunburn dose" of ultraviolet-B also produced significant epidermal hyperplasia and resulted in complete loss of heavily damaged basal cells within 4 d postirradiation. The occurrence and distribution of cyclobutane dimers in human skin correlated well with putative sunlight exposure and resembled that observed in ultraviolet-B-irradiated mice. Heavily damaged basal cells were observed at various sites, including those receiving sporadic sunlight exposure, suggesting that these cells may play an important role in carcinoma formation in humans.
authors.affiliation: Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park/Research Division, Smithville, Texas 78957, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Mitchell
authors.forename: B
authors.initials: B
authors.lastname: Volkmer
authors.forename: E W
authors.initials: EW
authors.lastname: Breitbart
authors.forename: M
authors.initials: M
authors.lastname: Byrom
authors.forename: M G
authors.initials: MG
authors.lastname: Lowery
authors.forename: R
authors.initials: R
authors.lastname: Greinert
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D004249:DNA Damage / Q000528:radiation effects*; D004817:Epidermis / Q000473:pathology* / Q000528:radiation effects*; D005260:Female; D006801:Humans; D051379:Mice; D014466:Ultraviolet Rays