The Micronucleus Assay in Toxicology


Book Description

Concerns about the adverse health effects of chemicals and radiation present in the environment and at workplaces have created the need for better detection systems to assess their potential to cause DNA damage in humans and other organisms across ecosystems. The Micronucleus Assay in Toxicology is the first comprehensive volume concerning the use of micronucleus assays in genetic toxicology. It succinctly explains the mechanisms by which genotoxins cause micronucleus formation and its relation to diseases. Furthermore, it describes the methods which are currently used for the analyses of micronuclei in different types of cells in human in vivo biomonitoring studies, routine in vivo tests with rodents, in vitro studies with human and mammalian cells, environmental monitoring with invertebrates and vertebrates such as molluscs, fish and, also, in plant bioassays. Moreover, this book also focuses on the use of the micronucleus technique in other research areas, including the detection of DNA damage caused by important groups of genotoxic carcinogens (heavy metals, industrial chemicals, cytotoxic drugs, pesticides, ionising radiation, etc.) as well as study designs, statistical analyses, international regulatory guidelines, and the development of automated scoring devices for this assay. This book will serve as both, a reference and a guide to students, and investigators in biomedical, biochemical and pharmaceutical sciences interested in gaining a better understanding of the biology of micronuclei and their application in measuring DNA damage caused by natural or man-made genotoxins.




Test No. 487: In Vitro Mammalian Cell Micronucleus Test


Book Description

The in vitro micronucleus test is a genotoxicity test for the detection of micronuclei in the cytoplasm of interphase cells. Micronuclei may originate from acentric chromosome fragments (i.e. lacking a centromere), or whole chromosomes that are ...




Genetic Toxicology Testing


Book Description

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




OECD Guidelines for the Testing of Chemicals, Section 4 Test No. 474: Mammalian Erythrocyte Micronucleus Test


Book Description

The mammalian in vivo micronucleus test is used for the detection of damage induced by the test substance to the chromosomes or the mitotic apparatus of erythroblasts, by analysis of erythrocytes as sampled in bone marrow and/or peripheral blood cells of animals, usually rodents (mice or rats).




The Micronucleus Assay in Toxicology


Book Description

Concerns about the adverse health effects of chemicals and radiation present in the environment and at workplaces have created the need for better detection systems to assess their potential to cause DNA damage in humans and other organisms across ecosystems. The Micronucleus Assay in Toxicology is the first comprehensive volume concerning the use of micronucleus assays in genetic toxicology. It succinctly explains the mechanisms by which genotoxins cause micronucleus formation and its relation to diseases. Furthermore, it describes the methods which are currently used for the analyses of micronuclei in different types of cells in human in vivo biomonitoring studies, routine in vivo tests with rodents, in vitro studies with human and mammalian cells, environmental monitoring with invertebrates and vertebrates such as molluscs, fish and, also, in plant bioassays. Moreover, this book also focuses on the use of the micronucleus technique in other research areas, including the detection of DNA damage caused by important groups of genotoxic carcinogens (heavy metals, industrial chemicals, cytotoxic drugs, pesticides, ionising radiation, etc.) as well as study designs, statistical analyses, international regulatory guidelines, and the development of automated scoring devices for this assay. This book will serve as both, a reference and a guide to students, and investigators in biomedical, biochemical and pharmaceutical sciences interested in gaining a better understanding of the biology of micronuclei and their application in measuring DNA damage caused by natural or man-made genotoxins.




Micronucleus Assay


Book Description

Micronucleus is defined as the small nucleus that forms whenever a chromosome or its fragment is not incorporated into one of the daughter nuclei during cell division. It is concluded that micronucleus assay can be used for risk prediction, screening, diagnosis and treatment of various chronic diseases. In this Micronucleus Assay: An Overview, the applications of micronucleus assay will be discussed. Ionisating radiations, ultraviolet rays, geogenic or anthropogenic pollutants can induce mutagenic, teratogenic or carcinogenic effects due to the induction of micro or macrolession over DNA. Several models have been used to measure the mutagenic and clastogenic effect of such agents. As such, the authors focus on one of these models: the micronucleus test. The micronucleus test can assess abnormalities earlier in the drug discovery pipeline, making structure/genotoxicity connection a possible system for drug characterization. Additionally, the authors provide knowledge about micronucleus assay and its usage in occupational toxicology studies. It is now recognized as one of the most successful and reliable assays for genotoxic carcinogens. The authors go on to present an overview of the evaluation of micronucleus assay by flow cytometry, reviewing the studies published in the international literature so far that employ different experimental designs for a variety of purposes. Humans can become exposed to a variety of chemical substances that can have adverse biological effects, and the sub-lethal genotoxicity can have the most far reaching and severe consequences like cancer or abnormal progeny as per the cell type involved. Hence, the penultimate chapter focuses on the significance of identifying and predicting potential genotoxic agents by using laboratory markers, thus regulating and preventing exposure to cancer causing agents In the concluding review, generation of micronucleus assay in the bone marrow cells of mice induced by various clastogenic chemicals, drugs, and radiation are elaborately elucidated. Bone marrow cells are easily susceptible to oxidative damage and sensitive to various clastogenic as well as aneugenic agents.




Genotoxicity Assessment


Book Description

Genetic toxicology is recognized by geneticists and researchers concerned with the genetic impact of man-made chemicals. In Genotoxicity Assessment: Methods and Protocols, expert researchers in the field provide comprehensive genetic toxicology protocols. These include in vitro and in vivo protocols on mutation assays, cytogenetic techniques, and primary DNA damage, assays in alternate to animal models, and updated ICH guidelines. Written in the highly successful Methods in Molecular Biology series format, the chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step and readily reproducible laboratory protocols, as well as key tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Genotoxicity Assessment: Methods and Protocols seeks to aid research students and scientists working in regulatory toxicology as well as biomedical, biochemical and pharmaceutical sciences.




Biological Dosimetry


Book Description

In October 1982, a small international symposium was held at the Gesellschaft fUr Strahlen- und Umweltforschung mbH (GSF) in Munich as a satellite meeting of the IX International Conference on Analytical Cytology. The symposium focussed on cytometric approaches to biological dosimetry, and was, to the best of our knowledge, the first meeting on this subject ever held. There was strong encouragement from the 75 attendees and from others to publish a proceedings of the symposium. Hence this book, containing 30 of the 36 presentations, has been assembled. Dosimetry, the accurate and systematic determination of doses, usually refers to grams of substance administered or rads of ionization or some such measure of exposure of a patient, a victim or an experimental system. The term also can be used to describe the quantity of an ultimate, active agent as delivered to the appropriate target material within a biological system. Thus, for mutagens, one can speak of DNA dosimetry, meaning the number of adducts produced in the DNA of target cells such as bone-mar row stem cells or spermatogonia.




Statistical Evaluation of Mutagenicity Test Data


Book Description

This rigorous and practical account of the interpretation of mutagenicity test data draws upon the expertise of toxicologists and statisticians. Chemicals, such as drugs, food additives and pesticides, all need careful screening to eliminate potentially mutagenic compounds.




Short-Term Tests for Chemical Carcinogens


Book Description

The recent surge of interest in designing, validating, and implementing short-term tests for carcinogens has been spurred by the fairly convincing correlation be tween the carcinogenicity and mutagenicity of chemicals and physical agents and by the assumption that DNA alteration, mutations, and chromosome aberrations are somehow involved in neoplastic transformation. Moreover, it has been tacitly assumed that the mutagenic capacity alone of compounds would induce regulatory agencies to pass rules for their removal from the environment and would lead the public to avoid them. The actual response, however, is quite different. Governmental departments shy away from making any decisions on the basis of in vitro test systems. The public at large is becoming irritated by daily an nouncements that many of their cherished habits could adversely affect their health. Industry appears to feel threatened and may reduce its search for new beneficial chemicals. The reluctance to accept wholeheartedly the mutagenicity tests for the detection of carcinogens is partly due to uncertainty about the in volvement of mutations in neoplastic transformation, partly due to the present difficulty of extrapolating results from various endpoints obtained on numerous organisms to man, and partly due to a multitude of complex events that lead in vivo to the evolvement of benign or malignant tumors.