Published in Comprehensive Toxicology
This chapter will describe the actions of the xenosensors peroxisome proliferator-activated receptor (PPAR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), arylhydrocarbon receptor (AhR), and nuclear factor (erythroid-derived 2) (NF-E2)-related factor-2 (Nrf2) that regulate gene expression of the foreign compound-metabolizing en...
Published in Comprehensive Toxicology
Tumor promotion involves the induction of a state of sustained proliferation, hyperplasia, chronic inflammation, and oxidative stress. This promotes the clonal expansion of initiated (DNA-mutated) cells to form tumors. Tumor promoters, which can be tissue specific, include chemical irritants, mechanical wounding, ultraviolet (UV) irradiation, infec...
Published in Comprehensive Toxicology
In the mammalian ovary, the development of follicles is a complex process that begins with the formation of primordial follicles and culminates either in a normal atretic degradation process or in the release of an oocyte for fertilization. Female reproduction depends, in part, on successful development of follicles. However, large numbers of toxic...
Published in Comprehensive Toxicology
Congenital heart defects (CHDs) are the most commonly diagnosed birth defect and their incidence is increasing. CHDs affect 0.7% of all live births, and this may represent an underestimate as cardiac screening of neonates is not performed routinely. While some CHDs are genetic in origin, a majority have unknown etiology, and thus environmental cont...
Published in Comprehensive Toxicology
The final stages of follicular and oocyte maturation, ovulation, and fertilization take place during a narrow window of time, typically less than 24 h in rodents. These events, which are a prelude to normal embryonic development, can potentially be targeted by environmental contaminants or pharmaceuticals in a variety of ways, resulting in infertil...
Published in Comprehensive Toxicology
Quinone reductases are a large group of enzymes that catalyze the reduction of quinones. NQO1 and NQO2 are the major mammalian quinone reductases that catalyze the reduction of quinones to hydroquinones. Both NQO1 and NQO2 are FAD-containing homodimers with similar catalytic mechanism and overlapping substrate specificities; however, major differen...
Published in Comprehensive Toxicology
The aryl hydrocarbon receptor (AHR) is a member of the PAS (Per-Arnt-Sim) superfamily of receptors, which mediate responses to environmental stresses such as hypoxia and circadian rhythm, and control basic physiologic processes like vascular development, learning, and neurogenesis. The AHR protein is the primary mediator of the toxic effects of the...
Published in Comprehensive Toxicology
A common theme in chemically induced mammalian toxicity is the ability of certain chemicals to mediate their effects through activation of members of the nuclear receptor superfamily or the aryl hydrocarbon receptor (AHR), a basic-helix-loop-helix PAS (Per-ARNT-Sim) ligand-activated transcription factor (TF). Activation in turn leads to a myriad of...
Published in Comprehensive Toxicology
Biotransformation within both the mother and her developing embryo and fetus can play a variety of important roles in determining developmental toxicity or teratogenicity. The mother’s metabolism of a drug or environmental chemical (xenobiotic) can determine its elimination, thereby regulating the maternal plasma concentration of the xenobiotic, wh...
Published in Biochemical and Biophysical Research Communications
There is significant human exposure to polycyclic aromatic hydrocarbons (PAHs), many of which are potent carcinogens. Cytochrome P450 (CYP)1A enzymes play key roles in the metabolic activation of PAHs to carcinogenic metabolites. We previously showed persistent induction of CYP1A enzymes by 3-methylcholanthrene (MC) in vivo in rodents. In this stud...
