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

Abstract

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.

• Authors: K Sterling, A Raha, E Bresnick
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 128 Issue 1 Pg. 18-24 (Sep 1994) ISSN: 0041-008X [Print] United States
• PMID: 8079350 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Benzopyrenes
• Carcinogens
• Carrier Proteins
• Ligands
• Benzo(a)pyrene
• benzo(e)pyrene
• Cytochrome P-450 Enzyme System
• Oxidoreductases
• Luciferases
• Cytochrome P-450 CYP1A1
• Methyltransferases
• Glycine N-Methyltransferase

Topics

• Animals
• Benzo(a)pyrene (metabolism, pharmacology)
• Benzopyrenes (metabolism, pharmacology)
• Carcinogens (metabolism)
• Carrier Proteins (metabolism)
• Cytochrome P-450 CYP1A1
• Cytochrome P-450 Enzyme System (biosynthesis, genetics, metabolism)
• Gene Expression Regulation, Enzymologic
• Genes, Reporter
• Glycine N-Methyltransferase
• Ligands
• Liver Neoplasms, Experimental (enzymology, metabolism)
• Luciferases (genetics, metabolism)
• Methyltransferases
• Mice
• Oxidoreductases (metabolism)
• Promoter Regions, Genetic
• Transfection
• Tumor Cells, Cultured (enzymology)