This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Morris, R. J. Articles by Slaga, T. J. Search for Related Content PubMed PubMed Citation Articles by Morris, R. J. Articles by Slaga, T. J.

Evidence That a Slowly Cycling Subpopulation of Adult Murine Epidermal Cells Retains Carcinogen¹

The University of Texas System Cancer Center, Science Park, Research Division, Smithville, Texas 78957

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 µCi). 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 µg 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 µg 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.

¹ Supported by NIH Grants CA 34890, CA 34962, and CA 34521.

² To whom requests for reprints should be addressed.

Received 9/23/85. Revised 2/24/86. Accepted 2/27/86.

This article has been cited by other articles:

				D. J. Kim, K. Kataoka, D. Rao, K. Kiguchi, G. Cotsarelis, and J. DiGiovanni Targeted Disruption of Stat3 Reveals a Major Role for Follicular Stem Cells in Skin Tumor Initiation Cancer Res., October 1, 2009; 69(19): 7587 - 7594. [Abstract] [Full Text] [PDF]

				E. Macias, P. L. Miliani de Marval, A. De Siervi, C. J. Conti, A. M. Senderowicz, and M. L. Rodriguez-Puebla CDK2 Activation in Mouse Epidermis Induces Keratinocyte Proliferation but Does Not Affect Skin Tumor Development Am. J. Pathol., August 1, 2008; 173(2): 526 - 535. [Abstract] [Full Text] [PDF]

				B. R. Stripp and S. D. Reynolds Maintenance and Repair of the Bronchiolar Epithelium Proceedings of the ATS, April 15, 2008; 5(3): 328 - 333. [Abstract] [Full Text] [PDF]

				V. Levy, C. Lindon, Y. Zheng, B. D. Harfe, and B. A. Morgan Epidermal stem cells arise from the hair follicle after wounding FASEB J, May 1, 2007; 21(7): 1358 - 1366. [Abstract] [Full Text] [PDF]

				J. G.W. Nijhof, C. van Pelt, A. A. Mulder, D. L. Mitchell, L. H.F. Mullenders, and F. R. de Gruijl Epidermal stem and progenitor cells in murine epidermis accumulate UV damage despite NER proficiency Carcinogenesis, April 1, 2007; 28(4): 792 - 800. [Abstract] [Full Text] [PDF]

				G. C. Schatteman, M. Dunnwald, and C. Jiao Biology of bone marrow-derived endothelial cell precursors Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H1 - H18. [Abstract] [Full Text] [PDF]

				S. J. Kim, S. Cheung, and M. K. Hellerstein Isolation of nuclei from label-retaining cells and measurement of their turnover rates in rat colon Am J Physiol Cell Physiol, June 1, 2004; 286(6): C1464 - C1473. [Abstract] [Full Text] [PDF]

				K. M. Braun, C. Niemann, U. B. Jensen, J. P. Sundberg, V. Silva-Vargas, and F. M. Watt Manipulation of stem cell proliferation and lineage commitment: visualisation of label-retaining cells in wholemounts of mouse epidermis Development, November 1, 2003; 130(21): 5241 - 5255. [Abstract] [Full Text] [PDF]

				F. Montanaro, K. Liadaki, J. Volinski, A. Flint, and L. M. Kunkel Skeletal muscle engraftment potential of adult mouse skin side population cells PNAS, August 5, 2003; 100(16): 9336 - 9341. [Abstract] [Full Text] [PDF]

				C. S. Potten, G. Owen, and D. Booth Intestinal stem cells protect their genome by selective segregation of template DNA strands J. Cell Sci., January 6, 2002; 115(11): 2381 - 2388. [Abstract] [Full Text] [PDF]

				D. J. Feith, L. M. Shantz, and A. E. Pegg Targeted Antizyme Expression in the Skin of Transgenic Mice Reduces Tumor Promoter Induction of Ornithine Decarboxylase and Decreases Sensitivity to Chemical Carcinogenesis Cancer Res., August 1, 2001; 61(16): 6073 - 6081. [Abstract] [Full Text] [PDF]

				M.-s. Tang, S. V. Vulimiri, A. Viaje, J. X. Chen, D. S. Bilolikar, R. J. Morris, R. G. Harvey, T. J. Slaga, and J. DiGiovanni Both ({+/-})syn- and ({+/-})anti-7,12-Dimethylbenz[a]anthracene-3,4-diol-1,2-epoxides Initiate Tumors in Mouse Skin That Possess -CAA- to -CTA- Mutations at Codon 61 of c-H-ras Cancer Res., October 1, 2000; 60(20): 5688 - 5695. [Abstract] [Full Text]

				H. Tani, R. J. Morris, and P. Kaur Enrichment for murine keratinocyte stem cells based on cell surface phenotype PNAS, September 26, 2000; 97(20): 10960 - 10965. [Abstract] [Full Text] [PDF]

				D. L. Mitchell, R. Greinert, F. R. de Gruijl, K. L. H. Guikers, E. W. Breitbart, M. Byrom, M. M. Gallmeier, M. G. Lowery, and B. Volkmer Effects of Chronic Low-Dose Ultraviolet B Radiation on DNA Damage and Repair in Mouse Skin Cancer Res., June 1, 1999; 59(12): 2875 - 2884. [Abstract] [Full Text] [PDF]

				V. A. Tron, M. J. Trotter, L. Tang, M. Krajewska, J. C. Reed, V. C. Ho, and G. Li p53-Regulated Apoptosis Is Differentiation Dependent in Ultraviolet B-Irradiated Mouse Keratinocytes Am. J. Pathol., August 1, 1998; 153(2): 579 - 585. [Abstract] [Full Text] [PDF]

				A. Li, P. J. Simmons, and P. Kaur Identification and isolation of candidate human keratinocyte stem cells based on cell surface phenotype PNAS, March 31, 1998; 95(7): 3902 - 3907. [Abstract] [Full Text] [PDF]

				M. Lehrer, T. Sun, and R. Lavker Strategies of epithelial repair: modulation of stem cell and transit amplifying cell proliferation J. Cell Sci., January 10, 1998; 111(19): 2867 - 2875. [Abstract] [PDF]

				I. Dardick and A. P. Burford-Mason Current Status of Histogenetic and Morphogenetic Concepts of Salivary Gland Tumorigenesis Critical Reviews in Oral Biology & Medicine, January 1, 1993; 4(5): 639 - 677. [Abstract] [Full Text] [PDF]