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Cellular and Molecular Toxicology

Volume 14

1st Edition - February 14, 2002

Editors: J.P. Vanden Heuvel, W.F. Greenlee, G.H. Perdew, William B. Mattes

Hardback ISBN:

9 7 8 - 0 - 4 4 4 - 5 0 8 6 8 - 3

Volume 14 in the series Comprehensive Toxicology extends and complements the previously published 13-volume set. This volume will be available separately.Toxicology is the study… Read more

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Volume 14 in the series Comprehensive Toxicology extends and complements the previously published 13-volume set. This volume will be available separately.

Toxicology is the study of the nature and actions of chemicals on biological systems. In more primitive times, it really was the study of poisons. However, in the early 1500s, it was apparent to Paracelsus that "the dose differentiates a poison and a remedy". Clearly, the two most important tenets of toxicology were established during that time. The level of exposure (dose) and the duration of exposure (time) will determine the degree and nature of a toxicological response.

Since that time the discipline of toxicology has made major advances in identifying and characterizing toxicants. The growth of toxicology as a scientific discipline has been driven to a large extent by the use of extremely powerful molecular and cell biology techniques. The overall 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.

A unique feature of this volume is its illustration of how carefully-designed studies of the molecular mechanisms of chemical action provide not only understanding of the potential toxicity of the chemical under investigation, but also new insights into the functioning of the biological system used as an experimental model. Each chapter contains a listing of major peer-reviewed articles and reviews and useful web-sites. In addition, each chapter contains a broad introductory section that outlines the subsequent sections. These Introductory and Overview sections are designed to be stand alone chapters, and may be packaged as a textbook in graduate level courses.

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.