Evidence that a slowly cycling subpopulation of adult murine epidermal cells retains carcinogen.
The distribution and persistence of radioactively labeled benzo(a)pyrene [B(a)P] in the skin of adult female SENCAR mice were investigated by autoradiography of epidermal whole mounts and cross-sections at intervals following a single initiating application of 200 nmol of either [3H]B(a)P (2 mCi) or [14C]B(a)P (23 muCi). One day after treatment, the entire thickness of the skin was labeled; the grain density was greatest over hair follicles, sebaceous glands, and interfollicular epidermis. At 1 and 2 weeks, decreases in the nuclear grain density were consistent with the overall pattern of epidermal renewal. One month after treatment, carcinogen label-retaining cells made up approximately 2% of the interfollicular basal cells. They were also present in the hair follicles, approximately 4 and 5% of basal cells in the infundibulum and external root sheath, respectively. They were rare in the germ region and dermal papilla. Carcinogen label-retaining cells were compared with slowly cycling [3H]thymidine label-retaining cells and "maturing" basal cells, two distinct proliferative subsets of adult murine epidermis. Carcinogen label-retaining cells were found to have characteristics of the slowly cycling cells: (a) most of the carcinogen labeled nuclei were found in the central regions of the epidermal proliferative units; (b) treatment of the carcinogen label-retaining cells with 2 micrograms of 12-O-tetradecanoylphorbol-13-acetate elicited labeled mitoses within 1 day, and a general decrease in grain density over basal nuclei. In contrast, maturing basal cells 4 days after a single injection of [3H]thymidine were found at the periphery of the epidermal proliferative units. Within 1 day after treatment with 2 micrograms of 12-O-tetradecanoylphorbol-13-acetate, maturing basal cells were displaced to the suprabasal layers. Double isotope-double emulsion autoradiographs demonstrated doubly labeled cells 1 month after continuous labeling with [3H]thymidine and [14C]B(a)P and provide evidence that the radioactive carcinogen is retained by the slowly cycling [3H]thymidine label-retaining cells. These observations suggest that a slowly cycling population of epidermal cells may be relevant to the initiation phase of two-stage carcinogenesis.
R J
RJ
Morris
S M
SM
Fischer
T J
TJ
Slaga
D000818:Animals; D001345:Autoradiography; D001564:Benzo(a)pyrene / Q000378:metabolism; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000378:metabolism*; D002455:Cell Division; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D012878:Skin Neoplasms / Q000139:chemically induced; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D002250:Carbon Radioisotopes; D002273:Carcinogens; D014316:Tritium; D001564:Benzo(a)pyrene; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine