Activation by Diverse Xenochemicals of the 51-Base Pair Phenobarbital-Responsive Enhancer Module in the CYP2B10Gene
- Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709
Abstract
By extending previous studies of the phenobarbital (PB)-responsive 132-base pair (bp) enhancer sequence in the CYP2B10gene, we have delimited a 51-bp enhancer element that is fully inducible by PB in mouse primary hepatocytes. Sixteen structurally unrelated phenobarbital-type inducers activated the 51-bp enhancer element in transient transfection assays. The results thus indicate that most PB-type inducers, if not all inducers, increase the transcription of the CYP2B10 gene by activating this 51-bp element, now designated PB-responsive enhancer module or PBREM.
Footnotes
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Send reprint requests to: Dr. Masahiko Negishi, Pharmacogenetics Section, Lab of Reproductive and Developmental Toxicology, NIEHS, NIH, Research Triangle Park, NC 27709. E-mail:negishi{at}niehs.nih.gov
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↵1 Current affiliation: Department of Pharmaceutics, University of Kuopio, FIN-70211 Kuopio, Finland.
- Abbreviations:
- P450
- cytochrome P450
- bp
- base pairs
- CAT
- chloramphenicol acetyltransferase
- DMSO
- dimethyl sulfoxide
- NFI
- nuclear factor I
- NR
- nuclear receptor
- PB
- phenobarbital
- PBREM
- phenobarbital-responsive enhancer module
- PCB
- polychlorinated biphenyl
- TCPOBOP
- 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene
- TK
- thymidine kinase
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- Received December 12, 1997.
- Accepted January 9, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
