FIG. 4.

Simulation of zonal induction of Cyp1A1 by TCDD. (A,B) Zonal induction profiles of Cyp1A1 and BAT at various doses of TCDD. (C) The zonation index, representing the percentage changes in Cyp1A1 expression across the lobule, relative to the TCDD doses. (D)Simplified diagram of the signaling pathway network to highlight the three main regulators of zonal Cyp1A1 induction by TCDD: Wnt signaling, negative feedback induced by Cyp1A2 binding to TCDD, and the cooperation of regulatory transcription factors β‐catenin and the BAT complex. (E) Zonal induction of Cyp1A1 in the model compared with immunostaining results at different doses of TCDD. Immunostaining pictures reproduced from Tritscher et al.⁽³⁾ Abbreviation: Cyp1A2_T, Cyp1A2‐TCDD molecular complex.