Differences in inducibility of CYP1A1-mRNA by benzimidazole compounds between human and mouse cells: Evidences of a human-specific signal transduction pathway for CYP1A1 induction

Hideaki Kikuchi, Hideaki Kato, Masayuki Mizuno, Anwar Hossain, Shuntaro Ikawa, Junichi Miyazaki, Minro Watanabe

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Three benzimidazole compounds, omeprazole (OP), thiabendazole (TBZ), and lansoprazole (LP), were compared with respect to the induction of CYP1A1- mRNA in human hepatoma cells, HepG2. OP was the most potent inducer among the three compounds, but LP was found to he a weak inducer. Induction by TBZ was at an intermediate level. None of these compounds induced CYP1A1-mRNA in a mouse hepatoma cell line, Hepa-1. The transient expression of mouse Cyp1a1- CAT gene into HepG2 cells showed that OP treatment of the transfectants induced CAT activity to the same degree as 2,3,7,8-tetrachlorodibenzo-p- dioxin treatment. Therefore, the cellular factors in human cells were able to work on the mouse regulatory element. The expression of human aryl hydrocarbon (Ah) receptor in the mouse Hepa-1 mutant cell line cl-19, which is defective in Ah receptor, did not increase the induction level of CYP1A1- mRNA by OP treatment. When the cultured medium of HepG2 cells in the presence of OP was added to the mouse Hepa-1 cell culture medium, CYP1A1-mRNA was not induced in Hepa-1 cells. It is thus concluded that metabolites of OP in human cells are not the ligands for the human Ah receptor. Therefore, in human cells, but not mouse cells, there must be an OP-sensitive activation factor for the human Ah receptor.

Original languageEnglish
Pages (from-to)235-240
Number of pages6
JournalArchives of Biochemistry and Biophysics
Volume334
Issue number2
DOIs
Publication statusPublished - 1996 Oct 15

Keywords

  • HepG2
  • benzimidazole
  • cytochrome P4501A1 (CYP1A1)
  • omeprazole

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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