(a)pyrene IB(a)Pl 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

The distribution and persistence of radioactively labeled benzo (a)pyrene IB(a)Pl 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 I3HIB(a)P (2 mCi) or f'4CJB(a)P(23 MCi).One day after treatment, the entire thickness of the skin was labeled the grain density was greatest over hair follicles, sebaceous glands, and interfofficular epidermis.At I and 2 weeks,decreases in the nuclear grain density were consistentwith the overallpattern ofepidermal renewal.One monthafter treatment,carcinogenlabel-retainingcellsmadeupapproximately2%of the interfollicularbasal cells. They werealso present in the hair follicles, approximately 4 and 5% of basal cells in the infundibulumand external root sheath, respectively.They were rare in the germ region and dermal papilla. Carcinogen label-retaining cells were compared with slowly cycling (3Hjthymidinelabel-retaining cells and “maturing― basal cells, two distinct proliferative subsetsof adult murine epidermis. Carcinogen label-retaining cells were found to have characteristics of the slowly cyclingcells: (a) most of the carcinogenlabeled nuclei were found in the central regions of the epidermal proliferative units (b) treatment of the carcinogenlabel-retaining cells with 2 @ig of 12-O-tetradecanoylphorbol 13-acetateelicited labeled mitoseswithin 1 day, and a generaldecrease in grain density over basal nuclei. In contrast, maturing basal cells 4 days after a single injection of f3Hjthymidine were found at the periphery of the epidermal proliferativeunits. Within 1 day after treatment with 2 sg of 12-O-tetradecanoylphorbol-13-acetate, maturing basal cells were dis placedto the suprabasallayers. Double isotope-doubleemulsionautora diographs demonstrated doubly labeled cells 1 month after continuous labeling with t3Hlthymidine and t―CIB(a)Pand provide evidence that the radioactive carcinogen is retained by the slowly cycling [3Hlthymidine 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.