8079350

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1

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.

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0041-008X

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18-24

pubmed-meshheading:8079350-Animals, pubmed-meshheading:8079350-Benzo(a)pyrene, pubmed-meshheading:8079350-Benzopyrenes, pubmed-meshheading:8079350-Carcinogens, pubmed-meshheading:8079350-Carrier Proteins, pubmed-meshheading:8079350-Cytochrome P-450 CYP1A1, pubmed-meshheading:8079350-Cytochrome P-450 Enzyme System, pubmed-meshheading:8079350-Gene Expression Regulation, Enzymologic, pubmed-meshheading:8079350-Genes, Reporter, pubmed-meshheading:8079350-Glycine N-Methyltransferase, pubmed-meshheading:8079350-Ligands, pubmed-meshheading:8079350-Liver Neoplasms, Experimental, pubmed-meshheading:8079350-Luciferases, pubmed-meshheading:8079350-Methyltransferases, pubmed-meshheading:8079350-Mice, pubmed-meshheading:8079350-Oxidoreductases, pubmed-meshheading:8079350-Promoter Regions, Genetic, pubmed-meshheading:8079350-Transfection, pubmed-meshheading:8079350-Tumor Cells, Cultured

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

Journal Article, Research Support, U.S. Gov't, P.H.S.