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Flow cytometry reveals subpopulations of murine epidermal cells that are refractory to induction of cytochrome P-4501A1 by beta- naphthoflavone

KL Stauber, JD Laskin, EJ Yurkow, PE Thomas, DL Laskin and AH Conney

Department of Chemical Biology and Pharmacognosy, College of Pharmacy, Rutgers, State University of New Jersey, Piscataway 08855-0789, USA.

Topical application of beta-naphthoflavone to CD-1 mice induced an 87- fold increase in epidermal 7-ethoxyresorufin O-dealkylation activity per cell and a many-fold increase in epidermal cytochrome P-4501A1 (CYP1A1) concentration. Flow cytometric analysis of individual epidermal cells from acetone-treated and beta-naphthoflavone-treated mice using a monoclonal antibody for CYP1A1 indicated that 50% to 60% of the isolated epidermal cells were refractory to beta-naphthoflavone induction of CYP1A1. Examination of the differences between responsive and nonresponsive epidermal cells from beta-naphthoflavone-treated mice revealed that 70% of the low CYP1A1-containing cells (noninduced) separated by flow cytometry were basal cells and only 12% were suprabasal differentiated cells. In contrast, about 50% of the high CYP1A1-containing induced cells separated by flow cytometry from the epidermis of mice treated with beta-naphthoflavone were suprabasal cells and 35% were basal cells. These results indicate that topical application of beta-naphthoflavone increased the level of CYP1A1 in about 80% of the separated suprabasal cells and in about 35% of the separated basal cells.

Volume 273, Issue 2, pp. 967-976, 05/01/1995
Copyright © 1995 by American Society for Pharmacology and Experimental Therapeutics




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