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About this book
About this book
The growth of toxicology has been driven to a large extent by the use of extremely powerful molecular and cell biology techniques. The aim of this volume is to demonstrate how these advances are being used to elucidate causal pathways (or linkages) for potential adverse health consequences of human exposure to environmental chemicals or radiation.
Preface. Contributors to Volume 14. Introduction. 1. Basic Concepts. Introduction to molecular toxicology. Exposure-Dose-Response: a molecular perspective. Receptor theory and the ligand-macromolecule complex. Control of gene expression. 2. Xenobiotic Receptor Systems. Introduction and overview. The Per-Arnt-Sim (PAS) protein superfamily. The Aryl hydrocarbon receptor: a model of gene-environment interactions. Peroxisomes, peroxisome proliferators and peroxisome proliferator-activated receptors (PPARs). The physiological role of Pregnane-X-Receptor (PXR) in xenobiotic and bile acid homeostasis. Regulation of phenobarbital responsiveness via the Constitutive Androstane Receptor (CAR). Mechanisms of metal-induction of metallothionein gene expression. Modulation of soluble receptor signaling by coregulators. Convergence of multiple nuclear receptor signaling pathways in the mediation of xenobiotic-induced nongenotoxic carcinogenesis. 3. Genetic Determinants of Susceptibility to Environmental Agents. Introduction and overview. Molecular biomarkers for human liver cancer. Inherited susceptibility and prostate cancer risk. Modeling genetic susceptibility to cancer in the mouse. DNA methylation and gene silencing. 4. Alterations of Cell Signaling by Xenobiotics. Introduction and overview. Mitogen-Activated Protein Kinase (MAPK) signal transduction pathways regulated by stresses and toxicants. Antioxidant induction of genes encoding detoxifying enzymes. Hypoxia regulation of gene expression through HIF1 signaling. Epigenetic-toxicant induced modulated gap junctional intercellular communication. Environmental influences on cell cycle regulation. Biochemical signals that initiate apoptosis. 5. Emerging Technologies and Predictive Assays. Introduction and overview. Bioinformatics. Interpretation of toxicogenomic data using genetically-altered mice. Gene expression analysis in the Microarray Age. Proteomic applications in toxicology. Metabonomic technology as a tool for rapid throughput in vivo toxicity screening. Data mining in toxicology. Appendix I.