THE DIFFERENTIATION-RELATED UP-REGULATION OF ARYL-HYDROCARBON RECEPTOR TRANSCRIPT LEVELS IS SUPPRESSED BY RETINOIC ACID

The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCD D) binds to a specific intracellular receptor protein -the Ah-receptor - which acts as a transcription factor. Herein we report on the relat ive levels of Ah-receptor-mRNA and TCDD-induced cytochrome P450 1A1 (C yp1A1)-mRNA and their modulation by retinoic acid in the human keratin ocyte cell line HaCaT. Ah-receptor-mRNA was already present in prolife rating keratinocytes and increased 8-fold in the course of differentia tion. Addition of 10 nM TCDD did not alter the level of Ah-receptor tr anscripts. In contrast, addition of 1 mu M RA maintained the amount of Ah-receptor-mRNA at the basal level as observed only in proliferating keratinocytes. The transcription of Cyp1A1 was dependent on TCDD-trea tment and increased fivefold in more differentiated cells as compared to proliferating cells. Simultaneous addition of retinoic acid reveale d an only twofold increase. These results indicate that the expression of the AhR is dependent on the state of differentiation of keratinocy tes and seems to be affected by retinoic acid. (C) 1995 Academic Press , Inc.