Characterization of human CYP1A1/1A2 induction by DNA microarray and α-naphthoflavone

Author： Ishida S.   Jinno H.   Tanaka-Kagawa T.   Ando M.   Ohno Y.   Ozawa S.   Sawada J-i.  

Publisher： Elsevier

ISSN： 0006-291X

Source： Biochemical and Biophysical Research Communications, Vol.296, Iss.1, 2002-08, pp. : 172-177

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Abstract

DNA microarrays and real time PCR were used to analyze the mechanism of gene induction by CYP1A1 inducers,β-naphthoflavone, and omeprazole, in the human hepatocellular carcinoma HepG2 cells. Reproducible and significant inductions were observed in a limited number of genes includingCYP1A1 and CYP1A2. Genes induced by omeprazole included several protein tyrosine kinase targets. This result confirmed that omeprazole could modulate gene expressions through protein tyrosine kinase-mediated pathway. Induction ratios were considerably different from CYP1A1 andCYP1A2 (>10-fold) to other induced genes (<5-fold).α-Naphthoflavone, which is known as an antagonist to 2,3,7,8-tetrachlorodibenzo-p-dioxin, inhibited the inductions of heme oxygenase 1, glutamate-cysteine ligase (modifier unit), and thioredoxin reductase byβ-naphthoflavone but not those of CYP1A1 and CYP1A2. It unexpectedly enhanced theβ-naphthoflavone-mediatedCYP1A1 and CYP1A2 induction. These results suggest that theCYP1A1 and CYP1A2 genes, which share their5′ enhancer regions, are regulated differently from the other genes.© 2002 Elsevier Science (USA)

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