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Mutagenicity -

Mutagenicity (eBook)

New Horizons in Genetic Toxicology

John A. Heddle (Herausgeber)

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2013 | 1. Auflage
490 Seiten
Elsevier Science (Verlag)
978-1-4832-7122-4 (ISBN)
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Mutagenicity: New Horizons in Genetic Toxicology provides an overview of the various applications and studies in the field of genetic toxicology and environmental mutagenesis. The book is composed of selected scientific papers written by experts in the field. The text presents topics on naturally occurring mutagens; occupational carcinogen; and evaluation of cooking methods. Experiments on mammalian cell mutation; chromosomal aberrations; and organisms that can be used as environmental monitors of toxicity are discussed as well. Ecologists, environmental and sanitary engineers, toxicologists, and anyone interested in environmental mutagenesis, genetic toxicology, occupational health, or the regulation of toxic substances will find the book a good source of insight.
Mutagenicity: New Horizons in Genetic Toxicology provides an overview of the various applications and studies in the field of genetic toxicology and environmental mutagenesis. The book is composed of selected scientific papers written by experts in the field. The text presents topics on naturally occurring mutagens; occupational carcinogen; and evaluation of cooking methods. Experiments on mammalian cell mutation; chromosomal aberrations; and organisms that can be used as environmental monitors of toxicity are discussed as well. Ecologists, environmental and sanitary engineers, toxicologists, and anyone interested in environmental mutagenesis, genetic toxicology, occupational health, or the regulation of toxic substances will find the book a good source of insight.

Front Cover 1
Mutagenicity: New Horizons in Genetic Toxicology 4
Copyright Page 5
Table of Contents 6
List of Contributors 14
Preface 16
Chapter 1. Screening Chemicals for Mutagenicity: Practices and Pitfalls 18
I. INTRODUCTION 19
II. TEST BATTERIES 21
III. POSSIBLE BASIS OF DIVERGENT ASSAY RESPONSES OBSERVED BETWEEN ASSAY SYSTEMS 21
IV. DESIGN, VALIDATION, AND USE OF TESTBATTERIES 27
V. PITFALLS IN THE USE OF MUTATION ASSAYS 37
VI. MUTAGENIC SYNERGISM AND PROTECTION 44
VII. GENOTOXIC THRESHOLD DOSE LEVELS 45
VIII. CONCLUSIONS 48
ACKNOWLEDGMENTS 49
REFERENCES 49
Chapter 2. Qualitative and Quantitative Comparisons between Mutagenic and Carcinogenic Activities of Chemicals 52
I. INTRODUCTION: ENVIRONMENTAL CHEMICALS IN HUMAN CARCINOGENESIS AND THE ROLE OF EXPERIMENTAL DATA IN THE ASSESSMENT OF RISK 53
II. COMPARISON BETWEEN DATA ON CARCINOGENICITY IN HUMANS AND RESULTS OF MUTAGENICITY AND OTHER SHORT-TERM TESTS 55
III. COMPARISONS BETWEEN DATA FROMLONG-TERM ANIMAL CARCINOGENICITY TESTS AND RESULTS OF MUTAGENICITY (SHORT-TERM) TESTS 63
IV. QUANTITATIVE CORRELATIONS BETWEENTHE CARCINOGENIC POTENCY OF CHEMICALS AND THEIR MUTAGENIC ACTIVITY 68
V. COMPARISON OF THE IN VITRO MUTAGENICITY AND THE IN VIVO COVALENT BINDING INDEX OF CHEMICAL CARCINOGENS 74
VI. FACTORS THAT MAY AFFECT THE ACTIVITY OF CARCINOGENIC CHEMICALS IN SHORT TERM TESTS AND IN EXPERIMENTAL ANIMALS 79
VII. CONCLUSIONS 82
ACKNOWLEDGMENTS 83
REFERENCES 83
Chapter 3. The Use of Mutagenicity to Evaluate Carcinogenic Hazards in Our Daily Lives 90
I. INTRODUCTION 90
II. EXPERIMENTAL STUDIES 92
III. CONCLUSIONS AND FUTURE STUDIES 101
REFERENCES 102
Chapter 4. Mutagenicity and Lung Cancer in a Steel Foundry Environment 106
I. INTRODUCTION 106
II. FOUNDRY MUTAGENICITY STUDY 108
III. RESULTS 114
IV. CONCLUSIONS AND DISCUSSION 123
ACKNOWLEDGMENTS 130
REFERENCES 130
Chapter 5. The Use of Mutagenicity Testing to Evaluate Food Products 134
I. INTRODUCTION 134
II. METHODOLOGY 135
III. MUTAGENS IN NONPROCESSED FOOD 140
IV. MUTAGENS FORMED DURING FOOD PREPARATION AND COOKING 143
V. MODEL BROWNING REACTIONS 146
VI. INTEGRATED MUTAGENIC LOAD OF DIETS 151
VII. OUTLOOK 154
REFERENCES 156
Chapter 6. Transformation of Somatic Cells in Culture 160
I. INTRODUCTION 161
II. IN VITRO AND IN VIVO STUDIES OF BASIC MECHANISM OF NEOPLASTIC TRANSFORMATION 162
III. TYPES OF CELL TRANSFORMATIONSYSTEMS 167
IV. REGULATORY AND COMMERCIAL USES OF NEOPLASTIC TRANSFORMATION ASSAYS 178
V. SUMMARY 180
REFERENCES 181
Chapter 7. Mutagenicity Testing with Cultured Mammalian Cells: Cytogenetic Assays 188
I. INTRODUCTION 189
II. CYTOLOGICAL END POINTS USED 190
III. METHODOLOGY 194
IV. COMPARISON BETWEEN CHROMOSOME ABERRATIONS AND SISTER CHROMATID EXCHANGES 199
V. TYPES OF LESIONS LEADING TO SISTER CHROMATID EXCHANGES AND/OR CHROMOSOMAL ABERRATIONS 200
VI. INFLUENCE OF TUMOR PROMOTERS OR INHIBITORS ON INDUCTION OF CHROMOSOMAL ALTERATIONS 201
VII. CHROMOSOMAL ALTERATIONS AND POINT MUTATIONS 202
VIII. MUTAGENIC COMPOUNDS ASSAYED BY CYTOGENETIC METHODS 203
IX. DETECTION OF CARCINOGENS 203
X. APPLICATION OF CYTOGENETIC TESTS TO DETECT HUMAN RECESSIVE DISORDERS 204
XI. DETECTION OF COMPLEMENTATION GROUPS OF RECESSIVE DISORDERS 205
XII. EFFECT OF COCULTIVATION OF TWO DIFFERENT TYPES OF CELLS 206
XIII. QUANTIFICATION OF THE BIOLOGICAL EFFECTS IN RELATION TO PRIMARY EFFECTS IN THE DNA 207
XIV. IN VITRO CYTOGENETIC ASSAYS TO DETECT MUTAGENS IN COMPARISON TO OTHER SHORT-TERM TESTS 207
XV. THE HUMAN LYMPHOCYTE 208
ACKNOWLEDGMENTS 221
REFERENCES 221
Chapter 8. Measurement of Mutations in Somatic Cells in Culture 232
I. IMPORTANCE OF USING MAMMALIAN CELLSIN CULTURE FOR MUTAGENESIS STUDIES 232
II. OVERVIEW OF SELECTED ASPECTS OF MAMMALIAN CELL MUTAGENESIS STUDIES 234
III. UTILIZATION OF MUTAGENESIS STUDIES WITH CULTURED MAMMALIAN CELLS 241
IV. CONCLUSION 247
ACKNOWLEDGMENT 247
REFERENCES 248
Chapter 9. Chromosomal Aberrations Induced in Occupationally Exposed Persons 258
I. INTRODUCTION: POSSIBILITIES OFFERED BY CYTOGENETIC METHODS FOR TESTING THE EFFECTS OF SMALL DOSES OF CHEMICALS APPLIED CHRONICALLY TO MAN 259
II. STUDIES OF WORKERS OCCUPATIONALLY EXPOSED TO CHEMICALS 265
III. OPEN QUESTIONS IN THE FIELD OF CYTOGENETIC MONITORING OF OCCUPATIONALLY EXPOSED PEOPLE 275
IV. CONCLUSIONS: SUMMARY OF CURRENT KNOWLEDGE AND FUTURE TRENDS 278
REFERENCES 279
Chapter 10. The Rationale and Methodology for Quantifying Sister Chromatid Exchange in Humans 284
I. RATIONALE FOR THE ANALYSIS OF SISTER CHROMATID EXCHANGE IN HUMANS 285
II. METHODOLOGICAL ASPECTS OF SISTER CHROMATID EXCHANGE ANALYSIS IN HUMAN POPULATIONS 290
III. STATISTICAL CONSIDERATIONS 300
IV. APPLICATION TO HUMAN STUDIES 314
ACKNOWLEDGMENT 316
REFERENCES 316
Chapter 11. The 6-Thioguanine-Resistant Peripheral Blood Lymphocyte Assay for Direct Mutagenicity Testing in Humans 322
I. INTRODUCTION 323
II. THE THIOGUANINE-RESISTANT (TGr) PBL ASSAY METHOD 328
III. SAMPLE RESULTS 332
IV. STATISTICAL ANALYSIS METHODS 336
V. DISCUSSION 346
ACKNOWLEDGMENTS 350
REFERENCES 350
Chapter 12. Sperm Assays as Indicators of Chemically Induced Germ-Cell Damage in Man 354
I. INTRODUCTION 354
II. DESCRIPTION OF AVAILABLE HUMAN SPERM ASSAYS AND THEIR RELATIVE SENSITIVITIES 355
III. REVIEW OF THE USES OF SPERM ASSAYS IN CHEMICALLY EXPOSED MEN 357
IV. RATIONALE, STRATEGIES, AND PROBLEMS ENCOUNTERED IN THE USE OF HUMAN SPERM ASSAYS IN EXPOSED POPULATIONS 361
V. THE IMPLICATIONS OF CHEMICALLYINDUCED SPERM CHANGES 363
VI. CONCLUSIONS 365
ACKNOWLEDGMENTS 366
REFERENCES 366
Chapter 13. Cytogenetic Events in Vivo 368
I. INTRODUCTION 368
II. STRUCTURAL CHROMOSOME ABERRATIONS 369
III. SISTER CHROMATID EXCHANGES (SCEs) 384
REFERENCES 394
Chapter 14. Dominant Skeletal Mutations:Applications in Mutagenicity Testing and Risk Estimation 402
I. INTRODUCTION 403
II. Dominant Skeletal Mutation Rate Experiment Using Breeding Tests 404
III. THE NEW SENSITIVE-INDICATOR METHOD 408
IV. OTHER MAJOR QUESTIONS ABOUT GENETIC RISK NOW AMENABLE TO STUDY 417
V. STUDY OF INDUCED DOMINANT DAMAGE TO OTHER BODY SYSTEMS 417
VI. EFFECTS OF DECREASED VIABILITY AND INCOMPLETE PENETRANCE ON EXPERIMENTAL FREQUENCIES OF INDUCED DOMINANT DAMAGE 418
VII. RELATIVE MERITS OF SENSITIVE INDICATOR AND STANDARD SPECIFIC LOCUS METHODS 419
VIII. SPECIAL CASE IN WHICH RISK ESTIMATION IS GREATLY SIMPLIFIED BYUSING SENSITIVE-INDICATOR AND SPECIFIC-LOCUS METHODS 420
ACKNOWLEDGMENTS 421
REFERENCES 421
Chapter 15. Plants as Sensitive in Situ Detectors of Atmospheric Mutagens 424
I. INTRODUCTION 425
II. Tradescantia as an in Situ System for the Detection of Atmospheric Mutagens 426
III. POLLEN SYSTEMS FOR THE DETECTION OF ATMOSPHERIC MUTAGENS 433
IV. OTHER HIGHER-PLANT MUTAGEN ASSAY SYSTEMS 436
V. THE USE OF IN SITU WEED COMMUNITIESFOR THE DETECTION OF ATMOSPHERIC MUTAGENS 442
VI. DISCUSSION AND CONCLUSIONS 445
ACKNOWLEDGMENTS 446
REFERENCES 446
Chapter 16. Fishes as Biological Detectors of the Effects of Genotoxic Agents 452
I. INTRODUCTION 452
II. METHODOLOGIES FOR AQUATI CGENETIC TOXICOLOGY 455
III. SUMMARY AND CONCLUSIONS 468
ACKNOWLEDGMENTS 469
REFERENCES 470
Index 474
CELL BIOLOGY: A Series of Monographs 489

Erscheint lt. Verlag 22.10.2013
Sprache englisch
Themenwelt Sachbuch/Ratgeber Gesundheit / Leben / Psychologie Krankheiten / Heilverfahren
Medizin / Pharmazie Gesundheitsfachberufe
Medizin / Pharmazie Medizinische Fachgebiete
Studium 2. Studienabschnitt (Klinik) Pharmakologie / Toxikologie
ISBN-10 1-4832-7122-6 / 1483271226
ISBN-13 978-1-4832-7122-4 / 9781483271224
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