Note: Cover -- Half Title -- Title Page -- Copyright Page -- Table of Contents -- Preface -- Editor Biography -- Contributors -- 1 Environmental Paradigm Change and Risk Assessment -- 1.1 Introduction -- 1.2 Risk Assessment -- 1.3 Uncertainties That May Hamper the Process of Evaluation of Risk -- 1.4 Historical Perspective and Current Approaches -- 1.4.1 General Outline of Environmental Risk Assessment in the European Union -- 1.4.2 General Outline of Environmental Risk Assessment in United States -- 1.5 Tools Used for Environmental Risk Assessment -- 1.5.1 European Union System for the Evaluation of Substances (EUSES) -- 1.5.2 European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) Targeted Risk Assessment (TRA) -- 1.5.3 EcoFate -- 1.5.4 Exposure Model for Soil-Organic Fate and Transport (EMSOFT) -- 1.6 Future Trends and Challenges -- Acknowledgments -- References -- 2 Environmental and Ecotoxicological Impacts of Engineered Nanomaterials -- 2.1 Introduction -- 2.2 Regulation of Nanomaterials Risk Assessment -- 2.3 Toxicity of Nanomaterials -- 2.4 Role of Physicochemical Properties in Nanoparticles Toxicity -- 2.4.1 Shape -- 2.4.2 Size -- 2.4.3 Surface Charge -- 2.4.4 Morphology -- 2.4.5 Degree of Agglomeration -- 2.5 Toxicity Mechanism in Natural Ecosystem Induced By Nanoparticles -- 2.6 Toxicity Mechanism in Plants Induced By Nanoparticles -- 2.6.1 Effect of Nanoparticles On Crop Quality -- 2.7 Mechanism of Plant-Nanoparticles Interaction -- 2.8 Nanoparticles Exposure to Humans via Potential Routes and Toxicity -- 2.8.1 Gastrointestinal Tract (GIT) -- 2.8.2 Respiratory Tract -- 2.9 Dermal Penetration -- 2.10 Conclusion -- Acknowledgement -- References -- 3 Toxicology of Metal Ions, Pesticides, Nanomaterials, and Microplastics -- 3.1 Introduction -- 3.1.1 Environmental Toxicology -- 3.2 Emerging Environmental Contaminants. , 3.2.1 Metal Ions -- 3.2.1.1 Routes of Exposure -- 3.2.1.2 Toxicity and Mechanism of Action -- 3.2.2 Pesticides -- 3.2.2.1 Routes of Exposure -- 3.2.2.2 Toxicity and Mechanism of Action -- 3.2.3 Nanomaterials -- 3.2.3.1 Routes of Exposure -- 3.2.3.2 Toxicity and Mechanism of Action -- 3.2.4 Micro- and Nanoplastics -- 3.2.4.1 Routes of Exposure -- 3.2.4.2 Toxicity and Mechanism of Action -- 3.3 Conclusion -- References -- 4 Natural Organic Matter: A Ubiquitous Adsorbent in Aquatic Systems to Probe Nanoparticles Behavior and Effects in Ecosystem -- 4.1 Introduction -- 4.2 Release of Engineered Nanomaterials in Environmental Matrices -- 4.3 Environmental Impact of Engineered Nanomaterials -- 4.3.1 Different Routes of Nanomaterial Exposure On the Aquatic Organisms -- 4.3.2 Fate of Engineered Nanomaterials in the Environment -- 4.3.3 Interactions Between the Natural Organic Matter and Engineered Nanomaterial -- 4.3.4 Effect of Natural Organic Matter in the Toxicity of the Nanoparticles to the Organisms and Food Chain -- 4.4 Trophic Transfer and Biomagnification Potential of Engineered Nanomaterial -- 4.5 Impact of Engineered Nanomaterials On the Producers of the Ecosystem -- 4.6 Conclusion -- Acknowledgments -- Note -- References -- 5 Analysis of Emerging Contaminants in Water Samples: Advances and Challenges -- 5.1 Introduction -- 5.2 Environmental Chemistry of Emerging Micro-Pollutants -- 5.3 Sampling, Extraction, and Quantification -- 5.3.1 Sample Collection -- 5.3.2 Sample Extraction -- 5.3.3 Sample Preparation Techniques -- 5.3.4 Water Analysis -- 5.3.5 Optimization of GC-MS/MS -- 5.3.6 Optimization of LC-HR/MS -- 5.4 Conclusions -- Acknowledgments -- Abbreviations -- References -- 6 Advanced Techniques for Detection of Environmental Pollutants and Recent Progress -- 6.1 Introduction. , 6.2 Basics of Traditional Environmental Pollutant Monitoring and Detections -- 6.3 Types of Environmental Pollutions -- 6.3.1 Air Pollution -- 6.3.2 Water Pollution -- 6.4 Detection of Environmental Pollutant By Instrumental Technique -- 6.4.1 Spectroscopy Techniques for Analysis -- 6.4.2 Separation Techniques for Analysis -- 6.5 Detection of Environmental Pollutants Using Nano-Enabled Sensors -- 6.5.1 Optical Method -- 6.5.2 Electrochemical Method -- 6.5.3 Magnetic Method -- 6.5.4 Paper-Based Detection Method -- 6.6 Conclusion and Future Perspective -- Acknowledgments -- References -- 7 Impact of Heavy Metals On Different Ecosystems -- 7.1 Introduction -- 7.2 What Are HMs? -- 7.3 Major HMs in the Environment -- 7.3.1 Cadmium (Cd) -- 7.3.2 Chromium (Cr) -- 7.3.3 Lead (Pb) -- 7.3.4 Mercury (Hg) -- 7.3.5 Arsenic (As) -- 7.4 HMs and Their Effects On Different Types of Ecosystem -- 7.4.1 Forest Ecosystem -- 7.4.2 Grassland Ecosystem -- 7.4.3 Fresh Water Ecosystem -- 7.4.4 Marine Ecosystem -- 7.4.5 Mangrove Ecosystem -- 7.4.6 Coral Reefs -- 7.5 Sources of HMs -- 7.6 Responsible Factors -- 7.6.1 Bio-Availability -- 7.6.2 Uptake -- 7.6.3 Bioaccumulation -- 7.6.4 Biomagnification -- 7.6.5 Tropic Transfer -- 7.7 Conclusion -- Acknowledgments -- References -- 8 Metabolism of Environmental Pollutants With Specific Reference to Pesticides, Endocrine Disrupters, and Mutagenic Pollutants -- 8.1 Introduction -- 8.2 Cytochrome P450 -- 8.3 Pesticides as an Environmental Pollutant -- 8.3.1 Adverse Effects of Pesticides -- 8.3.2 Routes of Entry for Pesticides -- 8.3.3 Metabolism of Pesticides -- 8.4 Metabolism of Endocrine Disruptors -- 8.5 Mutagenic Pollutants -- 8.6 Conclusion -- References -- 9 Bioavailability, Bioconcentration, and Biomagnification of Pollutants -- 9.1 Introduction -- 9.2 Food Chain and Food Web -- 9.2.1 Trophic Levels. , 9.2.2 Bioavailability, Bioconcentration, and Biomagnification - A Comparison -- 9.3 Pollutants -- 9.3.1 Heavy Metal Wastes -- 9.3.1.1 Bioavailability of Heavy Metals -- 9.3.1.2 Bioconcentration Or Bioaccumulation of Heavy Metals -- 9.3.1.3 Biomagnification of Heavy Metals -- 9.3.1.4 Radioactive Wastes -- 9.3.1.5 Bioavailability, Bioaccumulation, and Biomagnification of Radioactive Isotops of Metals -- 9.3.2 Organic Pollutants -- 9.3.2.1 Bioavaibility of Organic Pollutants -- 9.3.2.2 Bioaccumulation of Organic Pollutants -- 9.3.2.3 Biomagnification of Organic Pollutants -- 9.3.3 Microplastic Wastes -- 9.3.3.1 Bioavailability of Microplastics -- 9.3.3.2 Bioaccumulation Or Bioconcentration of Microplastics -- 9.3.3.3 Biomagnification of the Microplastics -- 9.3.4 Nanomaterial Pollutants -- 9.3.4.1 Bioavailability of Nanomaterials -- 9.3.4.2 Bioaccumulation Or Bioconcentration of Nanomaterials -- 9.3.4.3 Biomagnification of Nanomaterials -- 9.4 Conclusion -- References -- 10 High Throughput Approaches for Engineered Nanomaterial-Induced Ecotoxicity Assessment -- 10.1 Introduction -- 10.2 HTS: Experimental Design and Imaging Techniques -- 10.2.1 Cell-Based and Biochemical Assays for HTS -- 10.2.2 Imaging Techniques -- 10.3 HTS Contribution in Ecotoxicity -- Acknowledgments -- References -- 11 Impact of Heavy Metals On Gut Microbial Ecosystem: Implications in Health and Disease -- 11.1 Introduction -- 11.2 Heavy Metals -- 11.3 Gut-Microbiome -- 11.3.1 GMB: Modulation of Xenobiotics Exposures -- 11.3.2 GMB: Biosynthesis of Important Secondary Metabolites -- 11.4 The Bidirectional Relationship in HMs and GMB -- 11.4.1 Lead (Pb) -- 11.4.1.1 Pb and GMB -- 11.4.2 Chromium (Cr) -- 11.4.2.1 Cr and GMB -- 11.4.3 Cadmium (Cd) -- 11.4.3.1 Cd and GMB -- 11.4.4 Arsenic (As) -- 11.4.4.1 As and GMB -- 11.4.5 Mercury (Hg) -- 11.5 Future Prospectives and Conclusion. , References -- 12 Roadmaps for Environmental Protection and Sustainable Development -- 12.1 Introduction -- 12.2 Types of Freshwater Ecosystems and Their Ecological Roles -- 12.2.1 Lotic Ecosystems -- 12.2.2 Lentic Ecosystems -- 12.2.3 Wetland Ecosystems -- 12.2.4 Ground Water Table and Aquifers -- 12.3 Impacts On Freshwater Ecosystems -- 12.3.1 Urbanization -- 12.3.2 Climate Change -- 12.3.3 Introduction of Exotic Species -- 12.4 Roadmaps Towards Sustainable Development -- 12.4.1 Monitoring -- 12.4.1.1 Monitoring Water Quality -- 12.4.1.2 Monitoring Biodiversity -- 12.4.1.3 Monitoring Toxicity -- 12.4.1.4 Monitoring Using Molecular Biomarkers -- 12.4.2 Restoration -- 12.4.2.1 Restoration of Lotic Systems -- 12.4.2.2 Restoration of Lentic Systems -- 12.4.3 Protection and Sustainable Development -- 12.5 Future Goals and Conclusion -- Author Contributions -- References -- Index.

Note: Front Cover -- Bacterial Survival in the Hostile Environment -- Copyright Page -- Dedication -- Contents -- List of contributors -- 1 Mycobacterium tuberculosis adaptation to host environment -- Introduction -- M. tuberculosis adaptation to host immune system and oxidative stress -- Strategies to counter microbicidal effect of myeloid cells -- Microenvironment modulation by M. tuberculosis -- M. tuberculosis adaptations to acidic environment of phagolysosomes -- Mycobacterial adaptations to hypoxic environment -- M. tuberculosis adaptations to subsist heat shock -- M. tuberculosis adaptation to metal stress -- Conclusion -- References -- 2 Modulation of host pathways by Mycobacterium tuberculosis for survival -- Introduction -- Modulation of glycolytic flux -- Endoplasmic reticulum stress -- Modulation in host mitochondria -- Apoptosis -- Necrosis -- Phagosome maturation -- Autophagy Regulation -- Conclusion -- References -- 3 Signaling nucleotides in bacteria -- Introduction -- cyclic-di-AMP -- c-di-AMP signaling -- Regulation of potassium uptake by c-di-AMP -- (p)ppGpp -- (p)ppGpp signaling -- Regulation of antibiotic resistance by (p)ppGpp -- cyclic-di-GMP -- c-di-GMP signaling -- Regulation of biofilm formation by c-di-GMP -- Conclusions and perspectives -- References -- 4 The fish immune armaments in response to pathogen invasion-a tour inside the macrophages -- Introduction -- Immune organs and cell types of teleosts -- Characteristics of teleosts' macrophages -- Phagocytosis by macrophages -- Antigen presentation by macrophages -- Subcellular crosstalk of teleost macrophages -- Modalities of cell death -- Immune evasion strategies of microbial pathogen -- Conclusion -- References -- 5 Essential proteins for the survival of bacteria in hostile environment -- Introduction -- Hostile environment outside human host: extreme temperature. , Hostile environment within the human host -- I. Helicobacter pylori -- Urease activity for pH homeostasis as a survival strategy of H. pylori in highly acidic hostile environment -- Evasion of innate immune response with bacterial proteins (H. pylori) -- Evasion of adaptive immune response (H. pylori) -- II. Salmonella typhimurium -- Acid shock proteins for pH homeostasis as a survival strategy of S. typhimurium -- Evasion of innate immune response with bacterial proteins (S. typhimurium) -- Evasion of adaptive immune response (S. typhimurium) -- References -- 6 Kinases and phosphatases in bacterial survival in hostile environment -- Introduction -- Kinases and phosphatases in abiotic conditions -- Kinases and phosphatases in biotic conditions -- Two-component system in host immune evasion -- References -- 7 Antimicrobial resistance-a serious global threat -- Introduction -- Mechanism of action of probiotics, challenges faced, and their evolution -- Antimicrobial agents -- Antiseptics and disinfectants -- Antibiotics/antibacterial agents -- Action of antimicrobial agents -- Intruding with cell wall synthesis -- Hindrance of bacterial protein synthesis -- Termination of nucleic acid synthesis -- Inhibition of microbial metabolic pathways -- Disruption and increased permeability of cytoplasmic membrane -- Antimicrobial resistance -- Causes of antimicrobial resistance -- Mechanism of antimicrobial resistance -- Blockage of access to target -- Decreased permeability -- Increased efflux -- Alteration and safeguarding the targets -- Enzymatic degradation of antibiotics -- By hydrolysis -- Relocation of the chemical group -- Resistance versus persistence -- Transmission of resistance -- Transduction -- Conjugation -- Transformation -- Spread of antimicrobial resistance -- Conclusion and future prospects -- References. , 8 Combination of virulence and antibiotic resistance: a successful bacterial strategy to survive under hostile environments -- Introduction -- Cross coselection -- Coselection mediated by horizontal gene transfer -- Role of plasmids -- Role of integrative and conjugative elements -- Role of genomic islands -- Bacteriophage-mediated transduction -- Hypermutations -- Antibiotic tolerance and persistence -- Compensatory mutations -- Conclusion -- Acknowledgments -- References -- 9 Mechanisms of biofilm-based antibiotic resistance and tolerance in Mycobacterium tuberculosis -- Introduction -- What is biofilm? -- Origins of biofilm hypothesis -- Characteristics of biofilm -- How biofilm is formed? -- Adhesion of microbial cells -- Proliferation and maturation -- Biofilm dispersal -- Quorum sensing -- Drug resistance mechanisms of biofilm -- Escape from host defense mechanisms -- Persistence and drug tolerance: role of mycobacterial biofilms -- Extracellular polymeric substances: matrix and capsule -- Horizontal gene transfer -- Enzyme-mediated resistance -- Metabolic state of the organisms in the biofilm -- References -- 10 Biofilms: cities of microorganisms -- Introduction -- History of biofilms -- How are biofilms formed? -- Impact of biofilms on human -- Biofilms and food sector -- Mechanisms used by various microorganisms to form biofilm -- Biofilm by pathogenic microorganisms -- Pseudomonas -- Enterotoxigenic Escherichia coli -- Vibrio cholerae -- Salmonella -- Campylobacter jejuni -- Streptococcus mutans -- Veillonella parvula -- Biofilm by beneficial microorganisms (probiotics) -- Lactobacillus rhamnosus GG -- Bifidobacterium -- Strategies or future trends against biofilms -- Conclusion -- References -- 11 Biofilm: a coordinated response of bacteria against stresses -- Introduction -- Host-mounted stresses against bacteria -- Physical status. , Host-microbe interactions -- Host immune challenges and coordinated microbial response -- Innate immune system -- Adaptive immune system -- Complement and coagulation system -- Antimicrobial peptides -- Biofilms -- Quorum sensing -- Expression of toxins, specialized secretion systems -- Responses from extracellular bacteria -- Responses from intracellular bacteria -- Conclusion -- References -- 12 The bacterial communication system and its interference as an antivirulence strategy -- Introduction -- Quorum-sensing and quorum quenching -- The architecture of quorum-sensing circuits -- Quorum-sensing systems in bacteria -- Vibrio fischeri -- Pseudomonas aeruginosa -- Vibrio cholerae -- Vibrio harveyi -- Staphylococcus aureus -- Connecting the dots between interspecies and interkingdom circuits -- Quorum quenching -- Antivirulence strategies based on quorum quenching -- Controlling biofilms -- Prophylactic use -- Cocktail of quorum-sensing inhibitors (quorum-sensing inhibitor combination therapy) -- Combination of quorum-sensing inhibitors with antibiotics -- Immunotherapy as quorum-quenching agent -- Quorum-sensing inhibitor molecules as nutritional supplements -- Social cheaters as therapy -- Is there resistance to quorum-sensing inhibitors? -- Conclusion -- Acknowledgments -- Conflict of interest -- Author contributions -- References -- 13 Microbial adaptations in extreme environmental conditions -- Introduction -- Mechanism of adaptation of extremophiles -- Thermophiles -- Psychrophiles -- Acidophiles -- Halophiles -- Alkaliphiles -- Piezophiles -- Radiophiles -- Xerophiles -- Applications of extremophiles/extremozymes -- Conclusion -- References -- 14 Adaptation strategies of piezophilic microbes -- Introduction -- Effects of pressure on microbial cells and macromolecules -- Effect on the nucleic acids -- Effect on proteins. , Effect on membrane lipids -- Effect on the cells -- Effect on microbial motility -- Adaptation mechanisms in the piezophiles -- Genome -- Protein -- Membrane modification -- Metabolic adaptation -- Biotechnological applications -- Conclusion -- References -- 15 Survival and adaptation strategies of microorganisms in the extreme radiation -- Introduction -- Radiation and radio-resistance -- Role of ions in the radiation resistance -- DNA repair for the radiation survival -- Production of mycosporine-like amino acids -- Scytonemin biosynthesis and UV neutralization -- Bacterioruberin -- Radiation resistance in D. radiodurans -- Radiation resistance in eukaryotes -- Conclusion -- References -- 16 Adaptation strategies of thermophilic microbes -- Introduction -- Taxonomical diversity -- Bacteria -- Archaea -- Eukarya -- Effect of temperature on microbial cells -- Adaptation mechanism of thermophiles -- Modification of cell membrane -- Protein modification -- Genomic modification -- Modification of DNA and RNA -- Application of thermophiles and their enzymes -- Role in bioremediation -- Role in biotransformation -- Role in bioproduction -- Role in the medical field -- Conclusion -- References -- Index -- Back Cover.

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.

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