Breast cancer is the major cause of cancer death in women worldwide. High penetrance genes account for only 5% of cases, whereas polymorphic low penetrance genes acting in concert with lifestyle/environmental risk factors are likely to account for a much higher proportion. Genotoxic compounds implicated in human breast carcinogenesis include endogenous compounds, estrogens, and dietary or envir...

a Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Md., b Yale School of Public Health, New Haven, Conn., c Department of Epidemiology and Population Health, Albert Einstein College of Medicine, and d Division of Epidemiology, Department of Environmental Medicine, New York University School of Medicine, New York, N.Y., USA Publish...

The nonsteroidal antiestrogen tamoxifen is widely used in breast cancer treatment and is currently under evaluation as a chemopreventive agent for individuals at high risk of contracting the disease. The effects of tamoxifen administration on the expression of xenobiotic metabolizing enzymes in F344 rat liver have been investigated. Tamoxifen administration for 7 days produced a dose-dependent ...

A global proteomics approach was applied to model the hepatic response elicited by the toxicologically well-characterized xenobiotic phenobarbital (PB), a prototypical inducer of hepatic xenobiotic metabolizing enzymes and a well-known nongenotoxic liver carcinogen in rats. Differential detergent fractionation two-dimensional liquid chromatography electrospray ionization tandem mass spectrometr...

The aryl hydrocarbon receptor (AhR) is a signal-regulated transcription factor, which is canonically activated by the direct binding of xenobiotics. In addition, switching cells from adherent to suspension culture also activates the AhR, representing a nonxenobiotic, physiological activation of AhR signaling. Here, we show that the AhR is recruited to target gene enhancers in both ligand [isopr...

Nonalcoholic fatty liver disease (NAFLD), which is characterized by triglyceride deposition in hepatocytes resulting from imbalanced lipid homeostasis, is of increasing concern in Western countries, along with progression to nonalcoholic steatohepatitis (NASH), liver fibrosis, and cirrhosis. Previous studies suggest a complex, mutual influence of hepatic fat accumulation, NASH-related inflammat...

21 Xenobiotic metabolism has been proposed to play a role in modulating the rate of 22 aging. Xenobiotic-metabolizing enzymes (XME) are expressed at higher levels in 23 calorically restricted mice (CR) and in GH/IGF-I-deficient long-lived mutant mice. In this 24 study, we show that many phase I XME genes are similarly upregulated in additional 25 long-lived mouse models, including “crowded litt...

A variety of xenobiotic chemicals, such as polycyclic aromatic hydrocarbons (PAHs), aryl- and heterocyclic amines and tobacco related nitrosamines, are ubiquitous environmental carcinogens and are required to be activated to chemically reactive metabolites by xenobiotic-metabolizing enzymes, including cytochrome P450 (P450 or CYP), in order to initiate cell transformation. Of various human P450...

Drug discovery and development is a high-risk enterprise that requires significant investments in capital, time and scientific expertise. The studies of xenobiotic metabolism remain as one of the main topics in the research and development of drugs, cosmetics and nutritional supplements. Antihypertensive drugs are used for the treatment of high blood pressure, which is one the most frequent sym...

Although hepatocyte-like cells derived from human pluripotent stem cells (hPSC-HLCs) are considered a promising model for predicting hepatotoxicity, their application has been restricted because of the low activity of drug metabolizing enzymes (DMEs). Here we found that the low expression of xenobiotic receptors (constitutive androstane receptor, CAR; and pregnane X receptor, PXR) contributes t...