Mechanism of benzo[a]pyrene-induced Cyp1a-1 gene expression in mouse Hepa 1c1c7 cells: Role of the nuclear 6 s and 4 s proteins

M. Merchant, X. Wang, C. Kamps, R. Rosengren, V. Morrison, S. Safe

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Treatment of wild-type (wt) aryl hydrocarbon (Ah)-responsive mouse Hepa 1c1c7 cells with benzo[a]pyrene (B[a]P) caused a concentration-dependent induction of ethoxyresorufin O-deethylase (EROD) activity. In contrast, B[a]P was inactive as an inducer in Ah nonresponsive class 1 and class 2 mutant cell lines. In parallel experiments, the nuclear fractions from wt cells treated with 10-7 m [3H]B[a]P contained both the 4 s carcinogen binding protein and the 6 s (Ah receptor) complexes, whereas only the 4 s complex was present in the nuclear fraction of the class 2 mutant cells. The results obtained from cotreatment of wt Hepa 1c1c7 cells with 10-6 or 10-7 m B[a]P and 5 × 10-7 or 10-7 m 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) showed that MCDF inhibited the induction of EROD activity and Cyp1a-1 mRNA levels by B[a]P. Moreover, using 10-7 m [3H]B[a]P and unlabeled MCDF, it was shown that MCDF not only inhibited the induction response but also caused a concentration-dependent decrease in levels of the nuclear 6 s complex but not the 4 s complex. In contrast, in situ competition studies with unlabeled 10-6 m] benzo[ghi]-perylene (B[ghi]P) resulted in the elimination of the nuclear [3H]B[a]P 4 s complex (but not the 6 s complex); however, the EROD activity and Cyp1a-1 mRNA levels in cells treated with 10-7 m B[a]P in the presence or absence of 10-6 m B[ghi]P were not significantly different. These results indicate that the 4 s binding protein is not required for the induction of Cyp1a-1 gene expression in Hepa 1c1c7 cells and suggest that B[a]P and 2,3,7,8-tetrachlorodibenzo-p-dioxin induce Cyp1a-1 gene expression via a common mechanism which involves binding to the Ah receptor.

Original languageEnglish (US)
Pages (from-to)250-257
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume292
Issue number1
DOIs
StatePublished - Jan 1992

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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