Note: Front Cover -- MUTAGENICITY: ASSAYS AND APPLICATIONS -- MUTAGENICITY: ASSAYS AND APPLICATIONS -- Copyright -- CONTENTS -- LIST OF CONTRIBUTORS -- FOREWORD -- PREFACE -- ACKNOWLEDGMENTS -- 1 - Mutagenesis, Genetic Disorders and Diseases -- 1. INTRODUCTION -- 2. MUTAGENS -- 2.1 Physical Mutagens -- 2.2 Chemical Mutagens -- 2.3 Biological Mutagens -- 3. MUTATIONS -- 3.1 Break in Homologous Chromosome -- 3.2 Breaks in Nonhomologous Chromosomes -- 4. DNA DAMAGE RESPONSE AND REPAIR -- 5. DNA REPAIR PATHWAYS -- 5.1 Direct Repair -- 5.2 Single-Strand Break Repair -- 5.2.1 Base Excision Repair -- 5.2.2 Nucleotide Excision Repair -- 5.2.3 Mismatch Repair -- 5.2.4 Interstrand Cross-Linking Repair -- 5.3 Double-Strand DNA Breaks Repair -- 6. GENETIC DISORDERS AND DISEASES -- 6.1 Noonan Syndrome (OMIM 163950) -- 6.2 Costello Syndrome (OMIM 218040) -- 6.3 Cardio-Facio-Cutaneous Syndrome (OMIM 115150) -- 6.4 Hirschsprung Disease (OMIM 142623) -- 6.5 Hutchinsons-Gilford Progeria Syndrome (OMIM 176670) -- 6.6 Cancer -- 6.7 Parkinson Disease (OMIM 168600) -- 6.8 Alzheimer Disease (OMIM 104300) -- 6.9 Ataxia-Telangiectasia (OMIM 208900) -- 6.10 Seckel Syndrome (OMIM 210600) -- 6.11 Cockayne Syndrome (OMIM 216400) -- 6.12 Fanconi Anemia (OMIM 227650) -- 6.13 Bloom Syndrome (OMIM 210900) -- 6.14 Werner Syndrome (OMIM 277700) -- 6.15 Xeroderma Pigmentosum (OMIM 278700) -- 7. SUMMARY -- ACKNOWLEDGMENT -- REFERENCES -- 2 - Detection of Mutation in Prokaryotic Cells -- 1. INTRODUCTION -- 2. MATERIALS AND METHODOLOGIES -- 2.1 Preparation of Mammalian Liver S9 Fraction -- 2.1.1 Induction of Rat Liver Enzymes -- 2.1.2 Removal of Liver From Rats -- 2.1.3 Preparation of Liver S9 Fraction -- 2.2 Preparation of Reagents -- 2.2.1 Vogel-Bonner (VB Salt) Solution (50×) -- 2.2.2 Glucose Solution (10% W/V) -- 2.2.3 Minimal Glucose Agar Plates. , 2.2.4 Histidine-Biotin Solution (0.5mM) -- 2.2.5 Top Agar Supplemented With Histidine-Biotin Solution -- 2.2.6 Buffers for Metabolic Activation -- 2.2.6.1 Sodium Phosphate Buffer (0.1mM, pH 7.4) -- 2.2.6.2 To Activate the NADP Regenerating System in Presence of Liver S9 Fraction -- 2.3 Methodology -- 2.3.1 Culture Preparation -- 2.3.2 Genetic Analysis of the Tester Strains -- 2.3.3 Histidine and Biotin (his, bio) or Tryptophan (trp) Dependence -- 2.3.4 rfa (Deep Rough) Mutation -- 2.3.5 Treatment of Culture -- 2.3.6 Plating of Treated Culture -- 3. RESULT EVALUATION -- 4. RESULT INTERPRETATION -- 5. EXPERIMENTAL DESIGN -- 6. PRECAUTION -- REFERENCES -- FURTHER READING -- 3 - Detection of Gene Mutation in Cultured Mammalian Cells -- 1. INTRODUCTION -- 2. PCR-BASED MUTATION DETECTION -- 3. DETECTION OF MUTATIONS BY DENATURING GRADIENT GEL ELECTROPHORESIS -- 4. SINGLE-STRAND CONFORMATION POLYMORPHISM -- 5. HETERODUPLEX ANALYSIS -- 6. MICROARRAY -- 7. ARRAYED PRIMER EXTENSION TECHNOLOGY -- 8. SINGLE-BASE EXTENSION-TAGS TECHNOLOGY -- 9. ATOMIC FORCE MICROSCOPY -- 10. FLUORESCENCE IN SITU HYBRIDIZATION -- 11. DNA SEQUENCING -- 12. KARYOTYPING -- 13. HYPOXANTHINE PHOSPHORIBOSYL TRANSFERASE, THYMIDINE KINASE, AND XANTHINE-GUANINE PHOSPHORIBOSYL TRANSFERASE GENE MUTATION DET... -- 14. CONCLUSION -- ACKNOWLEDGMENT -- REFERENCES -- 4 - Chromosomal Aberrations -- 1. INTRODUCTION -- 2. CHARACTERISTICS OF HUMAN CHROMOSOMES -- 3. SOURCES OF SPECIMEN FOR CYTOGENETIC ANALYSIS -- 4. CYTOGENETIC ANALYSIS -- 5. TYPES OF CHROMOSOME ABERRATION -- 5.1 Numeric Chromosomal Aberration -- 5.1.1 Euploidy -- 5.1.2 Aneuploidy -- 5.2 Structural Chromosomal Aberration -- 5.2.1 Inversion -- 5.2.2 Translocation -- 5.2.3 Deletion -- 5.2.4 Duplication -- 5.2.5 Isochromosome -- 5.2.6 Ring Chromosome -- 6. MECHANISM OF THE FORMATION OF CHROMOSOME ABERRATION. , 7. CAUSES OF CHROMOSOME ABERRATION -- 7.1 Ionizing Radiation -- 7.2 Spontaneous dsDNA Break -- 7.2.1 Endogenous Reactive Oxygen Species -- 7.2.2 Topoisomerases -- 7.2.3 Replication Error -- 7.3 Chemicals -- 8. FREQUENCY OF CHROMOSOME ABERRATION -- 9. METHODS FOR DETECTION OF CHROMOSOMAL ABERRATION -- 9.1 Cytogenetic Testing -- 9.1.1 Chromosomal Aberration Test -- 9.1.2 Micronucleus Assay -- 9.1.2.1 Cytokinesis-Blocked Micronucleus Assay -- 9.1.2.2 Micronucleus Assay Using Flow Cytometry -- 9.1.3 Karyotyping -- 9.2 Molecular Cytogenetic Testing -- 9.2.1 Fluorescence In Situ Hybridization -- 9.3 Microarray Comparative Genomic Hybridization Testing -- 9.4 Prenatal Screening to Detect Fetal Abnormalities -- 10. CLINICAL MANIFESTATION OF CHROMOSOMAL ABNORMALITIES -- 10.1 Chromosomal Aberration and Spontaneous Abortions -- 10.2 Chromosomal Aberration and Cancer -- 10.3 Behavior Peculiarities Associated With Chromosomal Aberration -- 10.4 Changes in Course of Adolescence and Fertility -- 10.5 Pattern of Dysmorphic Signs in Chromosomal Aberration -- 10.6 Congenital Malformations and Chromosomal Aberration -- 11. APPLICATIONS OF CHROMOSOMAL ABERRATION ANALYSES -- 11.1 Radiation- and Chemical-Induced Cancer Risk Assessment -- 11.2 Genotoxicity Assessment of Environmental Chemicals -- 11.3 Testing of New Pharmaceuticals and Chemical Substances -- 12. FUTURE PERSPECTIVE -- 13. CONCLUSION -- REFERENCES -- 5 - In Vivo Cytogenetic Assays -- 1. INTRODUCTION -- 2. CYTOGENETIC END POINTS -- 3. TREATMENT PROTOCOLS -- 3.1 Selection of Animal Species, Number, and Sex of Animals -- 3.2 Dose Selection -- 3.3 Route of Administration -- 3.4 Proof of Exposure -- 3.5 Duration of Treatment and Sampling Time -- 3.5.1 Micronucleus Test -- 3.5.2 Chromosome Aberration Assay -- 4. ANALYSIS -- 4.1 Target Tissues Processing Staining and Scoring -- 4.1.1 Micronucleus Test. , 4.1.2 Chromosomal Aberration Test -- 4.2 Size of Samples and Statistical Power -- 4.2.1 Micronucleus Test -- 4.2.2 Chromosome Aberration Assay -- 4.3 Cytotoxicity Evaluations -- 4.4 Relevance of Historical Control Data -- 4.5 Data Interpretation and Criteria for a Positive/Negative Result -- 4.6 False-Positive Outcome -- REFERENCES -- 6 - Mutagenicity and Genotoxicity Testing in Environmental Pollution Control -- 1. INTRODUCTION -- 2. TYPES AND SOURCES OF POLLUTION -- 2.1 Air Pollution -- 2.2 Water Pollution -- 2.3 Soil Pollution -- 3. IMPACT OF ENVIRONMENTAL POLLUTION -- 3.1 Effect of Pollution on Ecosystem -- 3.2 Effect of Pollution on Humans -- 3.3 Mutagenic Effects of Environmental Pollution -- 4. NEED OF MUTAGENICITY ASSAYS TO ASSESS ENVIRONMENTAL POLLUTION -- 5. APPLICATION OF MUTAGENICITY ASSAYS TO CONTROL ENVIRONMENTAL POLLUTION -- REFERENCES -- 7 - Mutagens in Food -- 1. INTRODUCTION -- 2. ADDITIVES -- 2.1 Preservatives -- 2.2 Food Colors -- 2.3 Sweeteners -- 3. CONTAMINANTS -- 3.1 Mycotoxins -- 3.2 Pesticides -- 3.3 Metals -- 3.4 Intrinsic Dietary Components -- 4. ADULTERANTS IN FOOD -- 4.1 Edible Oils -- 4.2 Nonpermitted Food Colors -- 5. MUTAGENS PRODUCED AS AN OUTCOME OF FOOD PROCESSING -- 5.1 Acrylamide -- 5.2 Benzene -- 5.3 Heterocyclic Amines/Polycyclic Aromatic Hydrocarbons -- 5.4 Chloropropanols -- 5.5 Nitrosamines -- 5.6 Furan -- 6. SUMMARY -- ACKNOWLEDGMENTS -- REFERENCES -- 8 - Emerging Computational Methods for Predicting Chemically Induced Mutagenicity -- 1. INTRODUCTION -- 2. RELATIONSHIP BETWEEN MUTAGENS AND THEIR ABILITY TO CAUSE CANCER -- 3. CRUCIAL ASPECTS OF COMPUTATIONAL PREDICTIVE MODELING -- 4. IN SILICO TOOLS AND TECHNIQUES FOR CHEMICAL MUTAGENIC PREDICTION -- 4.1 Virtual Screening -- 4.2 Quantitative Structure-Activity Relationship -- 4.3 Molecular Docking -- 4.4 Molecular Dynamics Simulation. , 5. FRAMEWORK OF COMPUTATIONAL APPROACH FOR UNDERSTANDING MUTAGENICITY -- 5.1 Evaluation and Screening of Chemicals -- 5.2 Identification and Prediction of Mutagenicity -- 5.2.1 Expert System -- 5.2.2 Statistical Learning Methods -- 5.3 Analysis of Mutagens -- 5.3.1 Molecular Descriptors and Fingerprints -- 5.3.2 Substructures or Structural Alerts -- 5.3.3 Scaffold Analysis -- 5.4 Understanding Mechanism and Interaction of Mutagens -- 6. SUMMARY -- ACKNOWLEDGMENTS -- REFERENCES -- 9 - Overview of Nonclinical Aspects for Investigational New Drugs Submission: Regulatory Perspectives -- 1. INTRODUCTION -- 2. TARGET IDENTIFICATION -- 3. TARGET VALIDATION -- 4. HIT SERIES IDENTIFICATION -- 5. ASSAY DEVELOPMENT -- 6. HIT TO LEAD IDENTIFICATION -- 7. LEAD OPTIMIZATION -- 8. INVESTIGATIONAL NEW DRUG SUBMISSION -- 8.1 M4S(R2) Guidelines -- 8.2 Metabolites in Safety Testing for Investigational New Drug -- 8.3 Nonclinical Data Required for Exploratory Investigational New Drug Studies -- 8.4 Specific Concerns With Investigational New Drug Submission -- 9. CONCLUSIONS -- REFERENCES -- 10 - Mutagenicity Testing: Regulatory Guidelines and Current Needs -- 1. BACKGROUND -- 2. MUTAGENICITY ENDPOINTS -- 3. REGULATORY FRAMEWORK -- 4. REGULATORY STUDIES FOR MUTAGENICITY TESTING -- 4.1 In Vitro Studies -- 4.2 In Vivo Studies -- 5. REGULATORY REQUIREMENTS FOR REGISTRATION -- 5.1 Pesticides -- 5.2 Pharmaceuticals -- 5.2.1 Option 1 -- 5.2.2 Option 2 -- 5.2.3 Quantitative Structure-Activity Relationships Modeling of Pharmaceuticals -- 5.2.4 DNA Reactive Drug Impurities -- 5.2.5 Biotechnology-Derived Products -- 5.2.6 Concerns of Anticancer, Photogenotoxic, and Liposomal Drugs -- 5.3 Medical Devices -- 5.4 Food Additives Ingredients -- 5.5 Industrial Chemicals -- 5.6 Cosmetics -- 5.7 Nanomaterials -- 6. PREDICTIVE MUTAGENICITY TESTING. , 7. LIMITATIONS AND CHALLENGES OF MUTAGENICITY ASSESSMENT.