Mechanisms Of Cell Toxicity (advances In Molecular & Cell Biology) (v. 20)

Cell biology is a rapidly developing discipline which brings together many of the branches of the biological sciences which were separate in the past. The 20th century has witnessed the development of a huge and diverse range of tools and techniques (physical, chemical and biological) which have irrevocably changed the study of cell biology, making it cross boundaries, link the molecule with the organelle and the cellular response with the larger organism. These interrelations between cell structure and function at the molecular and subcellular level are the central connecting theme of this series. This volume takes for its theme the subject of cell toxicity beginning with a perspective on intercellular targets and including chapters on the cytoskeleton, the role of mitochondria and xenobiotic metabolism Cellular toxicology has entered a new era. No longer are we concerned only with necrotic cell death produced by severe, acute insult (often to multiple intracellular targets) leading to disruption of the cell membrane. New advances in molecular and cellular biology are allowing the dissection of mechanisms of cell death involving more subtle targets within the cell. Toxicology has been very important, not only in understanding the mechanisms, nature, and severity of toxicity and thereby helping in risk assessment, but toxicology has also played a very important role in helping to understand basic biological processes. Historically this has perhaps been most evident in the use of toxic agents to interfere with specific reactions in the body and hence help to dissect out the mechanisms of metabolic processes. For example, the use of chemical inhibitors was very important in understanding the process of oxidative phosphorylation, or the tricarboxylic acid cycle. More recent examples are seen herein where toxicology interfaces with, for example structural biology in the study of the cytoskeletal components and their interactions. Indirectly, an understanding of the mechanisms of endogenous protective systems also improves knowledge of basic cell biology. Toxic insult and manipulation of cell signalling and control mechanisms in cell growth and differentation also highlight how important the discipline of cell toxicity has been and will continue to be a major contributor to our understanding of basic issues in the biological and biomedical sciences. This book offers selected reviews of some of the principal molecular mechanisms of cell toxicity Content: Edited by Page iii Copyright page Page iv List of Contributors Pages vii-viii Introduction to Cell Toxicity: A Perspective on Intracellular Targets Original Research Article Pages ix-xiii J. Kevin Chipman The Role of Xenobiotic Metabolism in Cell Toxicity Original Research Article Pages 1-23 Spiridon Vamvakas Reactive Oxygen Species and their Cytotoxic Mechanisms Original Research Article Pages 25-73 M.D. Evans, H.R. Griffiths, J. Lunec Calcium, Glutathione, and the Role of Mitochondria in Cell Injury and Death Original Research Article Pages 75-117 Donald J. Reed The Cytoskeleton as a Target in Cell Toxicity Original Research Article Pages 119-144 Alan J. Hargreaves Cell Death via Interactions of Agents with DNA Original Research Article Pages 145-182 Jørn A. Holme, Richard Wiger, Jan K. Hongslo, Erik J. Søderlund, Gunnar Brunborg, Erik Dybing Mechanisms of Apoptosis Original Research Article Pages 183-229 Alison C. Bayly, Ruth A. Roberts, Caroline Dive Index Pages 231-241