Biochem Biophys Res Commun. 2002 Aug 9;296(1):172-7.  

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

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

Project Team for Pharmacogenetics, National Institute of Health Sciences, 1-18-1
Kamiyoga, Setagaya-ku, 158-8501, Tokyo, Japan. ishida@nihs.go.jp

DNA microarrays and real time PCR were used to analyze the mechanism of gene
induction by CYP1A1 inducers, beta-naphthoflavone, and omeprazole, in the human
hepatocellular carcinoma HepG2 cells. Reproducible and significant inductions
were observed in a limited number of genes including CYP1A1 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 and CYP1A2 (>10-fold) to other induced genes (<5-fold).
alpha-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 by
beta-naphthoflavone but not those of CYP1A1 and CYP1A2. It unexpectedly enhanced
the beta-naphthoflavone-mediated CYP1A1 and CYP1A2 induction. These results
suggest that the CYP1A1 and CYP1A2 genes, which share their 5(') enhancer
regions, are regulated differently from the other genes.

PMID: 12147246 [PubMed - indexed for MEDLINE]