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), 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.
Sterling
K
K
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755-3835.
Raha
A
A
Bresnick
E
E
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000494:pharmacology; D001580:Benzopyrenes / Q000378:metabolism / Q000494:pharmacology*; D002273:Carcinogens / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D050938:Glycine N-Methyltransferase; D008024:Ligands; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008780:Methyltransferases; D051379:Mice; D010088:Oxidoreductases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000201:enzymology
D001580:Benzopyrenes; D002273:Carcinogens; D002352:Carrier Proteins; D008024:Ligands; D001564:Benzo(a)pyrene; C026487:benzo(e)pyrene; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D008156:Luciferases; D019363:Cytochrome P-450 CYP1A1; D008780:Methyltransferases; D050938:Glycine N-Methyltransferase