MURINE CYP1A-1 INDUCTION IN MOUSE HEPATOMA HEPA-1C1C7 CELLS BY MYRISTICIN

Mouse hepatoma Hepa-1c1c7 (Hepa-l) cells were treated with myristicin to assess the role of myristicin in the process of Cyp1a-1 induction. Treatment of Hepa-l cells with myristicin increased Cyp1a-1 transcript ion in a dose-dependent manner as shown by analysis of 7-ethoxyresoruf in O-deethylase activity, Cypla-1 protein level, and Cypla-1 mRNA. Myr isticin, however, did not competitively displace [H-3]2,3,7,8-tetrachl orodibenzo-p-dioxin from the Hepa-l cytosolic aryl hydrocarbon (Ah) re ceptor in a competitive Ah receptor binding analysis using sucrose den sity gradient sedimentation and did not affect formation of DNA-protei n complexes between the Ah receptor and its DRE target in a gel mobili ty shift assay using oligonucleotides corresponding to DRE 3 of the Cy p1a-1. These results suggest that the induction of Cyp1a-1 gene expres sion by myristicin in Hepa-l cells might occur through an Ah receptor- independent pathway. (C) 1997 Academic Press.