Presence on human chromosome 10 of omeprazole-sensitivity gene whose product mediates CYP1A1 induction.
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.
Kikuchi
H
H
Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University School of Medicine, Sendai, Japan. hkikuchi@idac.tohoku.ac.jp
Fukushige
S
S
Shibazaki
M
M
Shiratori
Y
Y
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*
D001571:Benzoflavones; C011512:alpha-naphthoflavone; D019363:Cytochrome P-450 CYP1A1; D009853:Omeprazole