Toxicogenomics

The new field of toxicogenomics presents a potentially powerful set of tools to better understand the health effects of exposures to toxicants in the environment. At the request of the National Institute of Environmental Health Sciences, the National Research Council assembled a committee to identify the benefits of toxicogenomics, the challenges to achieving them, and potential approaches to overcoming such challenges. The report concludes that realizing the potential of toxicogenomics to improve public health decisions will require a concerted effort to generate data, make use of existing data, and study data in new waysâ€"an effort requiring funding, interagency coordination, and data management strategies.

Toxicogenomics is the integration of genomics to toxicology. This technology is a powerful tool for collecting information from a large number of biological samples simultaneously and thus it is very useful for large-scale screening of potential toxicants. Toxicogenomics: A Powerful Tool For Toxicity Assessment provides up-to-date state-of-the-art information presented by the recognized experts, and is therefore an authoritative source of current knowledge in this field of research. The potential link between toxicology, genetics and human diseases makes this book very useful to investigators in many and varied disciplines of science and toxicology. Topics covered include: mechanistic toxicogenomics analysis and interpretation of toxicogenomic data principles of data mining in toxicogenomics design issues in toxicogenomics studies sources of variability in toxicogenomic assays Escherichia coli stress response as a tool for detection of toxicity toxicogenomics as a tool to assess immunotoxicity toxicogenomics and ecogenomics for studying endocrine disruption and basic biology use of toxicogenomics as an early predictive tool for hepatotoxicity nutrigenomics: the application of genomic signatures in nutrition-related research application of toxicogenomics in drug discovery potential uses of toxicogenomic biomarkers in occupational health and risk assessment usefulness of toxicogenomics in the regulatory environment perspectives on toxicogenomics at the US Environmental Protection Agency Toxicogenomics: A Powerful Tool For Toxicity Assessment is an essential resource for research scientists currently engaged in toxicogenomics, and will also be of interest to researchers working in toxicology, genetics, medicine, pharmacology, and food sciences, and to regulators and risk assessors of drug, food, environmental and agricultural products.

Since the advent of cDNA microarrays, oligonucleotide array technology, and gene chip analysis, genomics has revolutionized the entire field of biomedical research. A byproduct of this revolution, toxicogenomics is a fast-rising star within toxicological analysis. Gathering together leading authors and scientists at the forefront of the field, An Introduction to Toxicogenomics provides a comprehensive overview of this new discipline. With a focus on toxicology, it introduces the basic principles of microarray/oligonucleotide array-based genomic analysis and explains how it fits into the field of biomedical research. These discussions provide an overview to the actual mechanics of the analyses themselves and offer insights on handling and quality control. Then the book features an important section on the basics of data analysis and clustering methods such as genetic algorithms. Finally, it covers the application of expression profiling in the field of toxicology and addresses the two fundamental types of analysis in detail, with sections dedicated to both mechanistic and predictive studies. Although toxicogenomics promises fast, efficient techniques and information-rich data, much of its potential remains untapped. An Introduction to Toxicogenomics consolidates the concepts underlying the field to provide a solid foundation from which to begin your research endeavors.

Functional genomics has come of age. No longer is it an adventure for the avant garde scientist, but it has become an increasingly standardized mainstream tool accessible to any modern biological laboratory. Toxicogenomics studies are now generating an avalanche of data that, with the aid of established informatics methodology, is being translated into biologically meaningful information. This is enabling us to start harvesting the benefits from years of investment in terms of technology, time, and (of course) money. It is therefore timely to bring together leading toxicologists with a wide variety of scientific aims in this book to demonstrate how microarray technology can be successfully applied to different research areas. This book transects biology from bacteria to human, from ecologically relevant sentinel organisms to well-characterized model species, and represents the full toxicogenomics arena from exploratory "blue sky" science to the prospects for incorporation into regulatory frameworks. * Reviews some of the first really fruitful studies made in this area * Covers different organisms ranging from humans to model species and environmental sentinels * Provides a broad view of the area, increasing its attractiveness to researchers working in a variety of specialties

Toxicogenomics: Principles and Applications fills the need for a single, thorough text on the key breakthrough technologies in genomics, proteomics, metabolomics, and bioinformatics, and their applications to toxicology research. The first section following a general introduction is on genomics and toxicogenomics, and qPCR. The next sections are toxicoproteomics and metabolomics. The final section covers bioinformatics aspects, from databases to data integration strategies. A practical resource for specialists and non-specialists alike, this book includes numerous illustrations that support the textual explanations. It offers practical guidance to investigators wishing to pursue this line of research, and lists key relevant software and Internet resources.

Some of what we know about the health effects of exposure to chemicals from food, drugs, and the environment come from studies of occupational, inadvertent, or accident-related exposures. When there is not enough human data, scientists rely on animal data to assess risk from chemical exposure and make health and safety decisions. However, humans and animals can respond differently to chemicals, including the types of adverse effects experienced and the dosages at which they occur. Scientists in the field of toxicogenomics are using new technologies to study the effects of chemicals. For example, in response to a particular chemical exposure, they can study gene expression ("transcriptomics"), proteins ("proteomics") and metabolites ("metabolomics"), and they can also look at how individual and species differences in the underlying DNA sequence itself can result in different responses to the environment. Based on a workshop held in August 2004, this report explores how toxicogenomics could enhance scientists' ability to make connections between data from experimental animal studies and human health.

Research over the past decade has demonstrated that TGx methods of various types can be used to discriminate modes of mutagenesis as a function of dose. TGx can quickly inform safety evaluation regarding potential mechanisms of conventional outcomes and can provide essential dose-response information. This can then be used to ascertain the sequence of key events in a putative mode of action as may apply in quantitative cancer risk assessment. With the increasing complexity of research in mode of action investigations it is important to gain a better understand of approaches to data integration and health risk assessment. Furthermore, it is essential to consider how novel test systems and newer methods and approaches may be used in future to gain a better understanding of mechanisms. Toxicogenomics in Predictive Carcinogenicity describes toxicogenomics methods in predictive carcinogenicity testing, mode of action and safety evaluation, and cancer risk assessment. It illustrates these methods using case studies that have yielded significant new information on compounds and classes of compounds that have proven difficult to evaluate using conventional methods alone. This book additionally covers current and potential toxicogenomic research using stem cells as well as new bioinformatics methods for drug discovery and environmental toxicology. This publication is an indispensable tool for postgraduates, academics and industrialists working in biochemistry, genomics, carcinogenesis, pathology, pharmaceuticals, food technology, bioinformatics, risk assessment and environmental toxicology.

Toxicogenomics is a new, dynamic and very promising field that can help optimize toxicity analyses and streamline research into active substances. It is of interest not only for basic research and development, but also from a legal and ethical perspective. Here, experts from all the fields mentioned will find solid information provided by an international team of experienced authors. With its approach as an interdisciplinary overview, it will prove particularly useful for all those needing to develop appropriate research strategies. The authors work for major research institutions, such as the Fraunhofer Institute of Toxicology and Experimental Medicine (Germany), the German Cancer Research Center, the National Institute of Environmental Health Science (USA), the National Institute of Health Science (Japan) or for companies like Affymetrix, Altana Pharma, Bayer, Boehringer Ingelheim, Bruker, Merck, Nimblegen, Novartis, and Syngenta. Coverage ranges from the technology platforms applied, including DNA arrays or proteomics, via the bioinformatics tools required, right up to applications of toxicogenomics presented in numerous case studies, while also including an overview of national programs and initiatives as well as regulatory perspectives. Walter Rosenthal, Director of the Research Institute for Molecular Pharmacology in Berlin, praises the book thus: "I would like to congratulate the publishers of this handbook, one that deals with a extremely hot topic. They have succeeded in gaining as authors leading representatives from this field. The Handbook impressively shows how modern genomic research is leading to rapid advances and new insights within toxicology."