title: Presence on human chromosome 10 of omeprazole-sensitivity gene whose product mediates CYP1A1 induction.
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 alpha-naphthoflavone (alphaNF) 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-respon- siveness 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.
authors.affiliation: Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University School of Medicine, Sendai, Japan. hkikuchi@idac.tohoku.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Kikuchi
authors.forename: S
authors.initials: S
authors.lastname: Fukushige
authors.forename: M
authors.initials: M
authors.lastname: Shibazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Shiratori
mesh_terms: D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D002460:Cell Line; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000235:genetics*; D003582:Cytogenetics; D004351:Drug Resistance / Q000235:genetics; D004790:Enzyme Induction; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008954:Models, Biological; D009853:Omeprazole / Q000494:pharmacology*
chemical_list: D001571:Benzoflavones; C011512:alpha-naphthoflavone; D019363:Cytochrome P-450 CYP1A1; D009853:Omeprazole