INDUCTION OF CYTOCHROME P4501A1
- 1 April 1999
- journal article
- review article
- Published by Annual Reviews in Annual Review of Pharmacology and Toxicology
- Vol. 39 (1) , 103-125
- https://doi.org/10.1146/annurev.pharmtox.39.1.103
Abstract
Cytochrome P4501A1 is a substrate-inducible microsomal enzyme that oxygenates polycyclic aromatic hydrocarbons, such as the carcinogen benzo(a)pyrene, as the initial step in their metabolic processing to water-soluble derivatives. Enzyme induction reflects increased transcription of the cognate CYP1A1 gene. The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin is the most potent known cytochrome P4501A1 inducer. Two regulatory proteins, the aromatic (aryl) hydrocarbon receptor (AhR) and the AhR nuclear translocator (Arnt), mediate induction. AhR and Arnt are prototypical members of the basic helix-loop-helix/Per-Arnt-Sim class of transcription factors. Mechanistic analyses of cytochrome P4501A1 induction provide insights into ligand-dependent mammalian gene expression, basic helix-loop-helix/Per-Arnt-Sim protein function, and dioxin action; such studies also impact public health issues concerned with molecular epidemiology, carcinogenesis, and risk assessment.Keywords
This publication has 133 references indexed in Scilit:
- Inhibition of the Transcription of CYP1A1 Gene by the Upstream Stimulatory Factor 1 in RabbitsJournal of Biological Chemistry, 1997
- Transcriptional activation by recruitmentNature, 1997
- Limitations of the toxic equivalency factor approach for risk assessment of TCDD and related compoundsTeratogenesis, Carcinogenesis, and Mutagenesis, 1997
- Activation of Hypoxia-inducible Transcription Factor Depends Primarily upon Redox-sensitive Stabilization of Its α SubunitJournal of Biological Chemistry, 1996
- Identification of a Novel Cis-acting Negative Regulatory Element Affecting Expression of the CYP1A1 Gene in Rat Epidermal CellsPublished by Elsevier ,1996
- Cancer Risk Assessment: Evolution of the ProcessPreventive Medicine, 1996
- Mechanistic aspects of dioxin actionChemical Research in Toxicology, 1993
- Acetyltransferases and susceptibility to chemicalsToxicology Letters, 1992
- cDNA cloning and structure of mouse putative Ah receptorBiochemical and Biophysical Research Communications, 1992
- U‐Shaped dose‐response curves: Their occurrence and implications for risk assessmentJournal of Toxicology and Environmental Health, 1990