Abstract
It is widely recognized that xenobiotic-metabolizing enzymes play a fundamental role in the basic processes of carcinogenesis and toxicity on one hand, and chemoprevention and drug efficacy on the other. Realization that different factors can profoundly affect the expression of these enzymes at the genome level has resulted in an enhanced appreciation of the importance these genes play in our modern industrialized age. There continues to be rapid proliferation of studies addressing the molecular regulation of these genes. The discovery of common signal transduction pathways and transcription factors that dictate tissue and developmental-specific expression, as well as variation in expression within a given tissue, suggest that there may be significant interaction among these various regulatory systems. This report is a summary of a symposium that was part of the Structure, Function and Regulation of Cytochromes P450 and Xenobiotic Metabolizing Enzymes satellite meeting of the 2000 joint meeting of the American Society for Biochemistry and Molecular Biology, the American Society for Pharmacology and Experimental Therapeutics, the French Pharmacological Society, and the Pharmacological Society of Canada held in Boston, Massachusetts. This symposium brought together several speakers who addressed specific receptor-mediated signal transduction pathways involved in the regulation of xenobiotic-metabolizing enzymes, as well as other molecular mechanisms whereby endogenous factors are involved in controlling tissue- and developmental-specific expression.
Footnotes
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Send reprint requests to: Ronald N. Hines, Ph.D., Department of Pediatrics, Birth Defects Research Center, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226-4801. E-mail: rhines{at}mcw.edu
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↵1 Current address: Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
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This work was supported in part by USPHS Grants CA53106 and ES60143 (R.N.H.); DC02640 and ES07462 (X.D.); DK54774 and ES04244 (R.A.P.); ES07800 and ES06639 (C.J.E.); and a University of Louisville School of Medicine grant (K.C.F.).
- Abbreviations used are::
- P450
- cytochrome P450
- AhR
- aryl hydrocarbon receptor
- bp
- base pair
- bHLH
- basic helix-loop-helix
- C/EBP
- CCAAT/enhancer binding protein
- CDK
- cyclin-dependent kinase
- CKI
- CDK inhibitor
- DHEA
- dehydroepiandrosterone
- EMAS
- electrophoretic mobility shift assay
- FMO
- flavin-containing monooxygenase
- GR
- glucocorticoid receptor
- GRE
- glucocorticoid-responsive element
- HNF
- hepatocyte nuclear factor
- NFI
- nuclear factor I
- NPTA
- nasal-predominant transcriptional activity
- PAS
- Period/Ah receptor nuclear translocator/Single-minded
- PPARα
- peroxisome proliferator-activated receptor alpha
- pRb
- retinoblastoma protein
- PXR
- pregnane X receptor
- t-Bu-DEX
- dexamethasonet-butyl acetate
- TCDD
- 2,3,7,8-tetrachlorodibenzo-p-dioxin
- TTF1
- thyroid transcription factor 1
- YY1
- ying yang 1
- Received December 1, 2000.
- Accepted February 2, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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