INDUCTION OF CYP1A1 GENE-EXPRESSION IN MOUSE HEPATOMA-CELLS BY BENZO[E]PYRENE, A LIGAND OF THE 4S POLYCYCLIC HYDROCARBON-BINDING PROTEIN

Hepa 1c1c7 (WT), TAOc1BP(r)c1 (CI), and BP(r)c1 (CII) mouse hepatoma c ells were exposed to benzo[e]pyrene (B[e]P) or benzo[a]pyrene (B[a]P). B[e]P induced activity of a rat CYP1A1 reporter gene construct (-3015 to +2545 bp) by 1.8- to 2-fold and 5-fold in WT and CI cells, respect ively. B[e]P caused a 2-fold induction of a truncated CYP1A1 reporter gene construct (-658 to +2545 bp) in WT cells and induced ethoxyresoru fin O-deethylase (EROD) activity by 24- and 13-fold in WT and CI cells . B[a]P also induced CYP1A1 reporter gene and EROD activity in these c ells. WT and CII cells had both 8S (Ah) receptor and 4S polycyclic hyd rocarbon (PAH)-binding activity, while CI cells exhibited a lower 4S b inding activity; 8S binding activity was not detected in CI cells unde r two separate binding conditions. 8S binding activity in the presence of sodium molybdate was 60-fold greater in WT cells than in CII cells . The absence of sodium molybdate resulted in a dramatic decrease of 8 S binding activity in WT cells. The ability of B[e]P to induce CYP1A1 promoter-reporter gene activity and EROD activity in WT and CI cells s uggested a role for the 4S PAH-binding protein in the induction of CYP 1A1. The lack of detectable 8S binding activity in CI cells was in con cert with this role. (C) 1994 Academic Press, Inc.