Induction of CYP1A1 by beta-naphthoflavone in IEC-18 rat intestinal epithelial cells and potentiation of induction by dibutyryl cAMP.
We have examined the inducibility of CYP1A1 by beta-naphthoflavone (BNF) in a rat intestinal epithelial cell line, IEC-18, and the associated interaction between cAMP and BNF. CYP1A1 was not constitutively expressed in IEC-18 cells. Upon treatment with BNF, CYP1A1 RNA, protein, and microsomal 7-ethoxyresorufin O-deethylase activity were detected. Treatment with dibutyryl cAMP resulted in a 2-fold increase in the extent of induction at both RNA and protein levels, with corresponding increases in CYP1A1 enzymatic activity. These results support the involvement of protein kinase A in Ah receptor-mediated induction of CYP1A1 and provide an in vitro model for further studies on the mechanisms underlying regional and cellular differences in the regulation of CYP1A1 gene expression in the small intestine.
Zhang
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Wadsworth Center, New York State Department of Health, Albany 12201-0509, USA.
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Dunbar
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Kaminsky
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D000818:Animals; D003994:Bucladesine / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D019324:beta-Naphthoflavone / Q000008:administration & dosage / Q000494:pharmacology*
D012333:RNA, Messenger; D019324:beta-Naphthoflavone; D003994:Bucladesine; D019363:Cytochrome P-450 CYP1A1