Presence on human chromosome 10 of omeprazole-sensitivity gene whose product mediates CYP1A1 induction

H. Kikuchi, S. Fukushige, M. Shibazaki, Y. Shiratori

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Previously, we showed that CYP1A1 expression can be induced by omeprazole (OP) in the human cell line HepG2, but not in the mouse cell line Hepa-1. Now we show induction of CYP1A1 by α-naphthoflavone (αNF) in Hepa-1 cells. This induction was inhibited by the tyrosine kinase inhibitor herbimycin A, but not by the aromatic hydrocarbon (Ah)-receptor antagonist PD98059, suggesting the presence of a ligand-independent signal-transduction pathway in the mouse cell line too. We utilized the lack of CYP1A1 induction by OP in Hepa-1 cells to map a putative human gene for OP-responsiveness in cell hybrids produced by fusion of Hepa-1 and HepG2 cells. OP-induced CYP1A1 expression was detected in four out of the 32 Hepa-1 x HepG2 cell hybrids analyzed. To help identify the gene locus, a radiation-hybrid cell (E11) was constructed. Use of reverse-fluorescence in situ hybridization revealed that these five cell lines commonly retained human chromosome 10p. These results suggest that the human gene for OP-responsiveness is present on chromosome 10p.

Original languageEnglish
Pages (from-to)51-57
Number of pages7
JournalCytogenetic and Genome Research
Volume97
Issue number1-2
DOIs
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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