Polymorphisms in many xenobiotic metabolizing enzymes occur leading to variation in the level of enzyme expression in vivo. Enzymes showing such polymorphisms include the cytochrome P450 enzymes CYP1A1, CYP1A2, CYP2A6, CYP2D6, and CYP2E1 and the phase two metabolism enzymes glutathione S-transferase MI (GSTMI) and arylamine N-acetyltransferase 2 (NAT2). In the past, these polymorphisms have bee...

The aryl hydrocarbon receptor (AHR) is an orphan nuclear receptor with a primary function of mediating xenobiotic metabolism through transcriptional activation of Phase I and Phase II drug-metabolizing enzymes. Although no high-affinity physiological activators of AHR have been discovered, the endogenous signaling of the AHR pathway is believed to play an important role in the development and f...

BACKGROUND: The constitutive androstane receptor (CAR, NR1I3) plays a key role in the transcriptional activation of genes that encode xenobiotic/steroid and drug metabolizing enzymes. RESULTS: The expression of CAR mRNA throughout the circadian rhythm is reported for the first time in phase with the clock gene Bmal1 and in antiphase with the clock-controlled gene Rev-erbalpha mRNAs, with a peak...

Research over the past decade has provided convincing evidence to support the premise that phytochemicals from the diet offer protection against cancer risk. A large number of dietary phytochemicals have been demonstrated to exhibit anticancer activities by interfering with multiple signaling pathways aberrant in cancer. These agents target a plethora of cellular molecules and molecular pathway...

The nuclear receptor constitutive active/androstane receptor (CAR) up-regulated expression of the apoptotic growth arrest and DNA-damage-inducible 45 beta (GADD45B) gene in HepG2 cells. Overexpression of GADD45B augmented CAR-mediated induction of the human CYP2B gene by the CAR activator 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) and coactivated CAR-dependent transcription of the NR1...

The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are two closely related and liver-enriched nuclear hormone receptors originally defined as xenobiotic receptors. PXR and CAR regulate the transcription of drug-metabolizing enzymes and transporters, which are essential in protecting our bodies from the accumulation of harmful chemicals. An increasing body of evidence s...

The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are two closely related and liver-enriched nuclear hormone receptors originally defined as xenobiotic receptors. PXR and CAR regulate the transcription of drug-metabolizing enzymes and transporters, which are essential in protecting our bodies from the accumulation of harmful chemicals. An increasing body of evidence s...

Human Pregnane X Receptor (also called NR1I2), a member of orphan nuclear receptor superfamily, maps to chromosome 3q11-13 with ten exons coding for 434 amino acids (Zhang et al., 2001). PXR is a xenobiotic sensor and acts as a transcription factor of drug metabolizing enzymes (DMEs) and drug transporters. It can potentially affect the efficacy of chemotherapeutic drugs given during cancer trea...