Induction of CYP1A1 gene expression in mouse hepatoma cells by benzo[e]pyrene, a ligand of the 4S polycyclic hydrocarbon-binding protein

• Published in: Toxicology and applied pharmacology Vol. 128; no. 1; p. 18
• Main Authors: Sterling, K, Raha, A, Bresnick, E
• Format: Journal Article
• Language: English
• Published: United States 01-09-1994
• Subjects: Animals; Benzo(a)pyrene - metabolism; Benzo(a)pyrene - pharmacology; Benzopyrenes - metabolism; Benzopyrenes - pharmacology; Carcinogens - metabolism; Carrier Proteins - metabolism; Cytochrome P-450 CYP1A1; Cytochrome P-450 Enzyme System - biosynthesis; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Gene Expression Regulation, Enzymologic; Genes, Reporter; Glycine N-Methyltransferase; Ligands; Liver Neoplasms, Experimental - enzymology; Liver Neoplasms, Experimental - metabolism; Luciferases - genetics; Luciferases - metabolism; Methyltransferases; Mice; Oxidoreductases - metabolism; Promoter Regions, Genetic; Transfection; Tumor Cells, Cultured - enzymology
• ISSN: 0041-008X
• DOI: 10.1006/taap.1994.1175

Hepa 1c1c7 (WT), TAOc1BPrc1 (CI), and BPrc1 (CII) mouse hepatoma cells 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, respectively. B[e]P caused a 2-fold induction of a truncated CYP1A1 reporter gene construct (-658 to +2545 bp) in WT cells and induced ethoxyresorufin 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 cells. WT and CII cells had both 8S (Ah) receptor and 4S polycyclic hydrocarbon (PAH)-binding activity, while CI cells exhibited a lower 4S binding activity; 8S binding activity was not detected in CI cells under 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 8S 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 suggested a role for the 4S PAH-binding protein in the induction of CYP1A1. The lack of detectable 8S binding activity in CI cells was in concert with this role.