Principles of genetic toxicology:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
New York u.a.
Plenum Pr.
1987
|
| Ausgabe: | 2. ed. |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | Literaturangaben |
| Beschreibung: | XVII, 284 S. Ill., graph. Darst. |
| ISBN: | 0306425327 |
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Datensatz im Suchindex
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|---|---|
| adam_text | Principles of
Genetic Toxicology
Second Edition
David JJrusick
Hazleton Laboratories
Kensington, Maryland
PLENUM PRESS • NEW YORK AND LONDON
Contents
FOREWORD BY ALEXANDER HOLLAENDER vii
PREFACE ix
Chapter 1
ORIGINS OF GENETIC TOXICOLOGY 1
Introduction 1
The Role of Genetic Toxicology in Health Effects Testing 3
History of Genetic Toxicology 4
Technology Transfer and Applied Genetics 5
The Components of Genetic Toxicology 6
References 9
Chapter 2
FUNDAMENTALS OF GENETIC TOXICITY 13
Introduction 13
Basic Genetics for Toxicologists t 13
Gene Structure 13
Gene Function 16
xi
xii CONTENTS
The Cell Cycle and Chromosome Mechanics in Somatic
and Germ Cells 22
Somatic versus Germ Cells 22
The Chromosome 23
The Mitotic Cell Cycle 26
Meiosis and Chromosome Mechanics 29
DNA Alterations Resulting in Genotoxic Effects in Cells:
Mechanisms and Categorization 33
A Classification Scheme for Genotoxic Effects 33
Significance of the Classes of Genotoxic Effects 44
Repair of DNA Damage 47
References 50
Chapter 3
THE CONSEQUENCES OF GENOTOXIC EFFECTS IN
HUMANS AND OTHER MAMMALS 53
Introduction 53
Gene Pool Consequences 54
Genomic Target in Human Cells 58
The Direct Effect of Mutagens on the Transmissible
Gene Pool 58
The Relationship of Genotoxic Effects to Other
Toxicologic Phenomena 67
False-Negative and -Positive Responses 71
Promoting Agents as False Negatives 73
Relationship of Potency between Mutagenicity Assays
and in Vivo Oncogenicity 75
References 76
Chapter 4
SCREENING CHEMICALS FOR GENOTOXIC PROPERTIES 79
Introduction and Background * 79
Definitions of Terms 81
Screening Tests 82
Hazard Assessment Tests J 83
Risk Analysis Tests 83
Characteristics of Adequate Screening Test Methods 84
The Type(s) and Number(s) of Endpoints Detected 85
CONTENTS xiii
The Metabolic Capability of the Test or Associated Activating
System 85
Test Reliability/Reproducibility 89
Test Transferability 90
Strategies for Building a Test Battery 90
General Philosophy 90
Specific Approaches 91
Conducting the Tests 93
General Criteria for Dose Selection 93
The Use of Controls in in Vitro and in Vivo Testing 99
Use of in Vivo Genetic Toxicology Assays 103
Stand-Alone Techniques 104
Expansion of Standard Toxicology Assays 105
Regulations Affecting Testing 107
Data Analysis and Interpretation 107
Primary Evaluation of Individual Tests 107
Evaluation Approaches for Batteries 108
The Ideal Test Battery 108
Interpretation of Results from Test Batteries 110
Summary 115
References 117
Chapter 5
GENETIC RISK ESTIMATION 121
Introduction 121
Definition of Risk Estimation 122
Estimates of Current Genetic Burdens in Humans 123
Secondary Factors Influencing Risk Analyses 124
Genotype 124
DNA Repair Capacity 124
Sex 125
Cell Type 125
Diet 126
Theoretical and Practical Considerations Important
to Risk Analysis , 127
Risk Estimation Method for Somatic and Germ Cells 129
Somatic Cell Risk 129
Germ Cell Risk % 133
Indirect Measurement Approach to Risk Estimation 133
Direct Measurement Approach to Risk Estimation 134
Alternative Indirect Methods 135
xiv CONTENTS
Dosimetry Issues in Risk Assessment 137
Relationship of the Route of Exposure to Total
Body Dose 137
Relationship of the Route of Exposure to Metabolism 138
Blood-Gonadal Barriers 139
Molecular Dosimetry 140
Gene Function Issues in Risk Assessment 142
Data Extrapolation Issues in Risk Analysis 143
Extrapolation of in Vitro Potency to in Vivo Response 144
Extrapolation from Species to Species 145
Threshold 146
Is Genetic Risk Important to Society? 148
References 149
Chapter 6
APPLICATIONS OF GENETIC TOXICOLOGY TO HUMAN AND
ENVIRONMENTAL MONITORING 155
Introduction 155
Environmental Monitoring 155
Occupational Monitoring Approaches 160
Occupational Monitoring Objectives 161
Cytogenetic Techniques 162
Chromosome Damage and Cancer 162
Interpretation of Human Monitoring Results 164
Application of Biotechnology Techniques to Human Monitoring 167
Immunoassays 168
32P-Postlabeling 169
DNA Probes 169
Summary 169
References 170
Chapter 7
THE GENETIC TOXICOLOGY LABORATORY 173
Introduction 173
Regulatory Requirements Affecting Laboratory Operations 175
Hazardous Waste Disposal 175
Guidelines 176
CONTENTS XV
Laboratory Design and Chemical Containment 176
Work Area Containment Methodology 176
General Laboratory Ventilation 177
Laboratory Exhaust Ventilation 177
Handling and Storage of Chemicals 180
Personnel Protection 182
Medical Surveillance Program 182
Protective Clothing 183
Respiratory Protection 184
Waste Disposal 186
Good Laboratory Practices Requirements 187
References 191
Chapter 8
DESCRIPTIONS AND EVALUATION OF GENETIC
TOXICOLOGY ASSAYS 193
General Classification of Genetic Toxicology Assays 193
Level of Assay Development 193
Description of Common Assays for Gene Mutation 194
Microbial 194
Mammalian Cells in Vitro 196
Insects 199
Mammals 200
Tests for Chromosome Aberrations 201
Microbial 201
Mammalian Cells in Vitro 201
Insect Tests for Chromosome Effects 202
Mammals 203
Tests for Primary DNA Damage 210
Microbial Tests 210
Insects
Cultural Mammalian Cells 211
SCE Analysis 214
In Vivo Mammalian Primary DNA Damage 214
In Vitro Cell Transformation 215
References 221
xvi CONTENTS
Chapter 9
APPLICATIONS FROM BIOTECHNOLOGY RESEARCH TO
GENETIC TOXICOLOGY 227
Introduction 227
Impact on Test Methods 228
Techniques of Interest 228
Production of DNA Probes and Synthetic Nucleotide
Sequences 228
Applications of DNA Probes in Genetic Toxicology 229
Gene Cloning 231
Application of Techniques to Genetic Toxicology 237
Assay Development 237
Human Monitoring 239
Site-Specific Mutagenesis 241
Associated Implications of Biotechnology 242
Gene Therapy 242
Oncogenes 245
References 254
Chapter 10
GENETIC TOXICOLOGY AND ITS ROLE IN THE STUDY OF
CONGENITAL MALFORMATIONS 257
Introduction 257
Congenital Malformation Risk 257
Origin of Congenital Malformations (Birth Defects) 257
Teratogenicity and the Male 261
Summary 263
References 263
APPENDIXES
Appendix A: S9 Homogenate and S9 Mix 265
Background 265
S9 Batch Variability
S9 Standardization 269
S9 Stability 269
CONTENTS xvii
S9 Storage 271
Other S9 Problems 272
References 274
Appendix B: Dose Selection for in Vivo Genetic Assays 275
References 276
Appendix C: Selection References and Reviews of Genetics and
Genetic Toxicology 277
INDEX 279
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| spelling | Brusick, David Verfasser aut Principles of genetic toxicology 2. ed. New York u.a. Plenum Pr. 1987 XVII, 284 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Literaturangaben Agents tératogéniques Genetica larpcal Mutagenèse chimique Mutagénicité Mutation (biologie) ram Toxicologie génétique ram Environmental Pollutants Genetic toxicology Mutagens Mutation Gentoxikologie (DE-588)4338045-1 gnd rswk-swf Gen (DE-588)4128987-0 gnd rswk-swf Toxikologie (DE-588)4060538-3 gnd rswk-swf Mutagenese (DE-588)4170881-7 gnd rswk-swf Gen (DE-588)4128987-0 s Toxikologie (DE-588)4060538-3 s DE-604 Mutagenese (DE-588)4170881-7 s Gentoxikologie (DE-588)4338045-1 s HEBIS Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=005068974&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Brusick, David Principles of genetic toxicology Agents tératogéniques Genetica larpcal Mutagenèse chimique Mutagénicité Mutation (biologie) ram Toxicologie génétique ram Environmental Pollutants Genetic toxicology Mutagens Mutation Gentoxikologie (DE-588)4338045-1 gnd Gen (DE-588)4128987-0 gnd Toxikologie (DE-588)4060538-3 gnd Mutagenese (DE-588)4170881-7 gnd |
| subject_GND | (DE-588)4338045-1 (DE-588)4128987-0 (DE-588)4060538-3 (DE-588)4170881-7 |
| title | Principles of genetic toxicology |
| title_auth | Principles of genetic toxicology |
| title_exact_search | Principles of genetic toxicology |
| title_full | Principles of genetic toxicology |
| title_fullStr | Principles of genetic toxicology |
| title_full_unstemmed | Principles of genetic toxicology |
| title_short | Principles of genetic toxicology |
| title_sort | principles of genetic toxicology |
| topic | Agents tératogéniques Genetica larpcal Mutagenèse chimique Mutagénicité Mutation (biologie) ram Toxicologie génétique ram Environmental Pollutants Genetic toxicology Mutagens Mutation Gentoxikologie (DE-588)4338045-1 gnd Gen (DE-588)4128987-0 gnd Toxikologie (DE-588)4060538-3 gnd Mutagenese (DE-588)4170881-7 gnd |
| topic_facet | Agents tératogéniques Genetica Mutagenèse chimique Mutagénicité Mutation (biologie) Toxicologie génétique Environmental Pollutants Genetic toxicology Mutagens Mutation Gentoxikologie Gen Toxikologie Mutagenese |
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