Flow cytometry reveals subpopulations of murine epidermal cells that are refractory to induction of cytochrome P-4501A1 by beta-naphthoflavone.
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.
Stauber
K L
KL
Department of Chemical Biology and Pharmacognosy, College of Pharmacy, Rutgers, State University of New Jersey, Piscataway 08855-0789, USA.
Laskin
J D
JD
Yurkow
E J
EJ
Thomas
P E
PE
Laskin
D L
DL
Conney
A H
AH
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D015153:Blotting, Western; D002469:Cell Separation; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects* / Q000201:enzymology; D005260:Female; D005434:Flow Cytometry; D066298:In Vitro Techniques; D051379:Mice; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System