Edited by J.P. Vanden Heuvel, Center for Molecular Toxicology and Carcinogenesis, Dept. of Veterinary Science, 226 Fenske Laboratory, Penn State University, University Park, PA 16802, USA W.F. Greenlee, CIIT Centers for Health Research, P.O. Box 12137, 6 Davis Drive, Triangle Park, NC 27709-2137, USA G.H. Perdew, Center for Molecular Toxicology and Carcinogenesis, Dept. of Veterinary Science, 227 Fens Laboratory, Penn State University, University Park, PA 16802, USA W.B. Mattes, Pharmacia and Upjohn, Predictive and Mechanistic Toxicology, Mail Stop 7228-300-523, 301 Henrietta Street, Kalamazoo, MI 49007-4940, USA
Description 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.
Contents 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.
Books and book related electronic products are priced in US dollars (USD), euro (EUR), and Great Britain Pounds (GBP). USD prices apply to the Americas. EUR prices apply in Europe. GBP prices apply to the UK and all other countries. Customers who order on-line from the Americas will be invoiced in USD and all other countries will be invoiced in GBP.
