Genetic Toxicology

Genetic Toxicology is a comprehensive book covering the historical perspective of genetic toxicology; basic mechanisms of mutations and chromosomal effects; health consequences of genetic damage, including cancer and inheritable mutations; properties of physical, chemical, and biological mutagens; risk assessment of human exposure to genotoxicants; and the current position of some government regulatory agencies in the United States on the issues of genetic toxicology. The book will be a useful reference for students and researchers in toxicology, genetics, cancer biology, and medicine who are interested in the basic and applied principles of genetic toxicology. It will also benefit industrial toxicologists, products registration specialists, and government regulatory specialists with responsibility for the safety evaluation of industrial and environmental agents.

The field of genetic toxicology has gone through remarkable development in the seven years since the appearance of the first edition of Principles of Genetic Toxicology. One branch of toxicology research, chemical mutagenesis, has been elucidated and expanded as a result of increased effort, testing, and the sharing of data. This expansion has occurred not only in the industrialized countries, but also in countries that are comparatively less advanced in scientific implementation. These developing countries have taken advan tage of the basic practical methods that were so well described in the first edition of this work. It is significant to note how many centers have been established throughout the world and are now studying the basic concepts and applying them to practical problems such as the detection of genetic effects caused by exposure to chemicals. In fact, there are now toxicology training centers in twelve countries. Genetic toxicology, in addition to being investigated as a science unto itself, has been taught to people in the applied fields so that these techniques may be put to use in solving other biological problems. For these reasons, it is most useful to have an update of the basic methods and their development. Dr. Brusick should be congratulated for doing such an excellent job of assembling a text that will be worthwhile to any researcher who is interested in the principles of genetic toxicology. Alexander Hollaender Council for Research Planning in Biological Sciences, Inc. Washington, D. C.

The evaluation of potential mutagenic activity is a critical step in the assessment of the safety of both new and pre-existing chemical types. In Genetic Toxicology: Principles and Methods, expert contributors help to satisfy the demand for education in this tremendously important area of study. The volume covers three basic areas: the scientific basis of the discipline, the methodologies of the main test assays, and the application of the methods, all aimed primarily at scientists in the safety departments of the industries working with both natural and synthetic chemicals. Written in the highly successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Intuitive and cutting-edge, Genetic Toxicology: Principles and Methods provides crucial support to both laboratory workers in providing quality information on the appropriate application of techniques and to study directors in their assay selection and protocol design in this vital field.

Genetic Toxicology Testing: A Laboratory Manual presents a practical guide to genetic toxicology testing of chemicals in a GLP environment. The most commonly used assays are described, from laboratory and test design to results analysis. In a methodical manner, individual test methods are described step-by-step, along with equipment, suggested suppliers, recipes for reagents, and evaluation criteria. An invaluable resource in the lab, this book will help to troubleshoot any assay problems you may encounter to optimise quality and efficiency in your genetic toxicology tests. Genetic Toxicology Testing: A Laboratory Manual is an essential reference for those new to the genetic toxicology laboratory, or anyone involved in setting up their own. Offers practical and consistent guidance on the most commonly-performed tests and procedures in a genetic toxicology lab Describes standard genetic toxicology assays, their methodology, reagents, suppliers, and analysis of their results Includes guidance on general approaches: formulation for in vitro assays, study monitoring, and Good Laboratory Practice (GLP) Serves as an essential reference for those new to the genetic toxicology laboratory, or anyone involved in setting up their own lab

Presents state-of-the-art regulatory cancer risk assessment models including a biologically based model for two-hit carcinogenesis and cell proliferation! This book comprehensively reviews the various roles of genetic toxicology in human cancer risk assessment conducted by United States and worldwide regulatory agencies-discussing hazard identification, dose-response relationships, exposure assessment, and current practices of risk characterization. Examines predictive values of mutagenicity tests, mechanisms of carcinogenesis, and conventional genotoxicity tests required by the International Conference on Harmonization and the Organization for Economic Cooperation and Development/Environmental Protection Agency guidelines! Comprised of contributions from prominent experts and risk assessors and including nearly 1200 references to facilitate further study, Genetic Toxicology and Cancer Risk Assessment reviews contemporary human cancer genetics as related to the mutagenic nature of carcinogenesis calculates acceptable exposure levels based on a carcinogenic threshold dose for nongenotoxic carcinogens reveals the rationale and methodology of quantitative estimation of human cancer risks using mathematical models discusses the threshold concept of carcinogenesis demonstrates how bacterial mutagenicity assays are the most reliable for predicting rodent carcinogens considers structural activity relationship (SAR) analysis of chemical carcinogenicity describes the emergence of the mouse lymphoma microwell and in vitro micronucleus assays illustrates the use of genetic biomarkers for dosimetry analysis and more! Linking human cancer genetics, mutagenicity assays, mechanisms of carcinogenesis, carcinogenic thresholds, molecular epidemiology, mathematical modeling, and quantitative cancer risk analysis, Genetic Toxicology and Cancer Risk Assessment is a must-have reference for toxicologists; oncologists; geneticists; biostatisticians; reproductive, developmental, cell, and molecular biologists; endocrinologists; biochemists; and upper-level undergraduate, graduate, and medical school students in these disciplines.

To meet the needs of an ever-growing world population for food and fiber, agriculture uses an arsenal of chemicals to control insects, weeds and other pests that compete with man in the agricultural arena. In addition to their intended effect, many of these biologically active materials affect non-target organisms including man himself. There is concern about the resulting occupational exposure of those who work in agriculture and the environmental health of those who live in rural areas. Unintended side effects from the use of agricultural chemicals are further complicated by the dispersal of these substances well beyond the area of immediate use, through food chains, atmospheric transport, irrigation runoff, percolation to and diffusion through ground water, sometimes giving rise to public health and environmental problems at a distance from the place of application. In addition to toxic substances introduced into the agro ecosystem by man, one must be concerned about naturally occurring agents including mfcotoxins, plant poisons, infective biological agents and the levels of certain heavy metals. The formation of toxic substances, many of them mutagenic, during cooking and other processing of food is a related problem. While acute effects are more immediate and somewhat readily discerned, chronic and genetic effects tend to be more obscure and sometimes surface in a crisis situation long after substantial damage has been sustained. Genotoxicity assays and epidemiological studies play increasing roles in predicting and evaluating long term effects of low-level exposure to toxic materials.

Contained in this volume are the proceedings of the international conference on the "Genetic Toxicology of Complex Mixtures," held from July 4-7, 1989, in Washington, DC. This meeting was a satellite of the "Fifth International Conference on Environmental Mutagens" and the seventh in a biennial series of conferences on "Short-term Bioassays in the Analysis of Complex Environmental Mixtures. " Our central objective in calling together key researchers from around the world was to extend our knowledge of the application of the methods of genetic toxicology and analytical chemistry in the evaluation of chemical mixtures as they exist in the environment. This conference emphasized the study of genotoxicants in air and water, and the assessment of human exposure and cancer risk. The latest strategies and methodologies for biomonitoring of genotoxicants (including transformation products) were described in the context of the ambient environment. Source character ization and source apportionment were discussed as an aid to understand ing the origin and relative contribution of various kinds of complex mix tures to the ambient environment. Similarly, investigations of genotoxi cants found in the indoor environment (sidestream cigarette smoke) and in drinking water (chlorohydroxyfuranones) were given special attention in terms of their potential health impacts. New molecular techniques were described to enable more precise quantitation of internal dose and dose to-target tissues. The emphasis of presentations on exposures/effects assessment was on integrated quantitative evaluation of human exposure and potential health effects.