Molecular and Biochemical Toxicology, 5th

From the Publisher
Written as an advanced text for toxicology students, this book is much more than an introduction and provides in-depth information describing the underlying mechanisms through which toxicants produce their adverse responses.
•Links traditional toxicology to modern molecular techniques, important for teaching to graduate courses and professional studies
•Uses a didactic approach with basic biological or theoretical background for the methodology presented
•Brings together and comprehensively covers a range of dynamic aspects in biochemical and molecular toxicology
•Guides student and professional toxicologists in comprehending a broad range of issues, compiled and authored by a diverse group of experts
•“A good introductory textbook covering the biochemical toxicology of organic substances and the relevant methodology in some detail.... It offers good value for money and can be recommended as a textbook for appropriate courses” – BTS Newsletter review of the 4th edition

Table of Contents
Section 1 Introduction
1 Molecular and Biochemical Toxicology: Definition and Scope
1.1 Introduction
1.2 Sources of Information
1.3 Toxicology
1.4 Molecular and Cellular Toxicology
1.5 Proteomics and Metabolomics
1.6 Role of Molecular, Cellular, and Biochemical Toxicology: Implications for Risk Assessment
1.7 Conclusions
Suggested Reading
Section 2 Techniques in Biochemical and Molecular Toxicology
2 Molecular Techniques for the Study of Gene Function
2.1 Applicability of Molecular Techniques to Toxicology
2.2 Overview of Genes, Chromatin, and Their Relationship
2.3 Approaches to Characterize the Functions of Genes
2.4 Gene Targeting Technologies
2.5 Analysis of Gene Expression and Regulatory Mechanisms
2.6 Methods to Evaluate Gene Function in an Animal Model
References
Suggested Reading
3 Transcriptomics
3.1 Introduction
3.2 Cellular Organization and the Transcriptome
3.3 RNA Isolation
3.4 Platforms for Transcriptome Analysis: Microarrays
3.5 RNA]seq: NextGen Sequencing of the Transcriptome
3.6 Validation of Transcriptome Analysis
3.7 Analysis of Gene Expression Data
3.8 Summary
References
4 Proteomics
4.1 Introduction to Proteomics
4.2 Mass Spectrometry
4.3 Quantitation of Proteins by LC]MS/MS
4.4 Emerging Research Areas in Proteomics
4.5 Summary
Suggested
Reading
5 Metabolomics
5.1 Introduction
5.2 Endogenous and Exogenous Metabolites
5.3 Study Design and Experimental Considerations
5.4 Applications of Metabolomics
5.5 Technologies for Targeted and Broad]Spectrum Metabolomics
5.6 Statistical and Multivariate Analysis and Pathway Mapping
5.7 Summary
Acknowledgment
References
6 Cellular Techniques
6.1 Introduction
6.2 Cellular Studies in Intact Tissue
6.3 Studies
6.4 Monolayer Cell Culture
6.5 Observation of Cultured Cells
6.6 Indicators of Toxicity
6.7 Important Considerations and Advances
6.8 Replacement of Animal Testing with Cell Culture Models
6.9 Conclusion
Suggested Reading
Journals
7 Basic Concepts of Molecular Epidemiological Research Methods
7.1 Introduction
7.2 Molecular Epidemiology
7.3 Descriptive Epidemiologic Study Designs
7.4 Analytic Epidemiologic Studies
7.5 Experimental Studies
7.6 Inferring Causality from Molecular Epidemiologic Data
7.7 Summary
References
Suggested Reading
Reading Materials Related to Examples
Section 3 Mechanisms in Molecular and Biochemical Toxicology
8 Phase I and Phase II Metabolism and Metabolic Interactions: A Summary
8.1 Introduction
8.2 Metabolic Enzymes
8.3 Phase I Reactions
8.4 Phase II Reactions
8.5 Reactive Metabolites
8.6 Factors Affecting Metabolism
8.7 Synergism and Potentiation
8.8 Biphasic Effects
8.9 Environmental Effects
8.10 Human Variation in Toxicant Metabolism
8.11 Summary of Toxicant Metabolism
Suggested
Reading
9 Structure, Mechanism, and Regulation of Cytochromes
9.1 Introduction
9.2 Complexity of the Cytochrome 450 Gene Superfamily
9.3 Cytochrome P450 Structure
9.4 Mechanisms of P450 Catalysis
9.5 Cytochrome P450 Regulation
9.6 Transgenic Animal Models
9.7 Reactive Oxygen Species
9.8 Posttranslational Modification of P450s
9.9 Summary
Suggested
Reading
10 Polymorphisms in Phase I and Phase II Genes and Outcomes
10.1 Introduction
10.2 Toxicogenetics and Single Nucleotide Polymorphisms (SNPS)
10.3 Polymorphic Cytochrome P450 and Xenobiotics Metabolism
10.4 Other Polymorphic Phase I Genes and Xenobiotics Metabolism
10.5 Polymorphisms: Mechanistic Classification
10.6 Methods for the Study of Polymorphisms
10.7 Phase II Gene Polymorphisms and Xenobiotics Metabolism
10.8 Regulation of Phase II Genes Via Antioxidant Responsive Element
Suggested
Reading
11 Cellular Transport and Elimination
11.1 Transport as a Determinant of Xenobiotic Action
11.2 Factors Affecting Membrane/Tissue Permeability
11.3 Xenobiotic Transporters
11.4 Altered Xenobiotic Transport
Suggested
Reading
12 Nuclear Receptors
12.1 Introduction
12.2 NR Structure Function
12.3 Nomenclature
12.4 NR Transactivation
12.5 NRS in Toxicology
12.6 Endobiotic and Xenobiotic Metabolism
12.7 Defining New NR Targets for Toxicity: Toxcast and Tox21
Reference
Suggested Reading
13 Mechanisms of Cell Death
13.1 Introduction
13.2 How Cells/Tissues React to “Stress”
13.3 Cell Injury and Cell Death
13.4 Morphology of Cell Injury and Cell Death
13.5 Apoptosis, Morphology, and Mechanisms
13.6 Other Cell Death Modalities
Acknowledgments
Reference
Suggested Reading
14 Mitochondrial Dysfunction
14.1 Introduction
14.2 Mitochondrial Function
14.3 Mitochondrial Apoptosis/Necrosis
14.4 Toxicant]Induced Mitochondrial Apoptosis/Necrosis
References
15 Reactive Metabolites, Reactive Oxygen Species (ROS), and Toxicity
15.1 Introduction
15.2 Enzymes Involved in Bioactivation
15.3 Stability of Reactive Metabolites
15.4 Factors Affecting Metabolic Balance and Toxicity
15.5 Reactive Oxygen Species (ROS) and Toxicity
Suggested
Reading
16 DNA Damage and Mutagenesis
16.1 Introduction
16.2 Endogenous DNA Damage
16.3 Environmental DNA Damage
16.4 Concepts of Mutagenesis
16.5 Mechanisms of DNA Damage]Induced Mutagenesis
Suggested
Reading
17 DNA Repair
17.1 Introduction
17.2 Direct Reversal of Base Damage
17.3 Base Excision Repair
17.4 Nucleotide Excision Repair
17.5 Mismatch Repair
17.6 Recombinational Repair
17.7 DNA Repair and Chromatin Structure
17.8 DNA Repair in Mitochondria
17.9 DNA Repair and Cancer
17.10 Summary
Reference
Suggested Reading
18 Carcinogenesis
18.1 Introduction
18.2 Human Cancer
18.3 Categorization of Agents Associated with Carcinogenesis
18.4 Somatic Mutation Theory
18.5 Epigenetic Mechanism of Tumorigenesis
18.6 Multistage Tumorigenesis
18.7 Oncogenes
18.8 Tumor Suppressor Genes
18.9 Mutator Phenotype/DNA Stability Genes
18.10 Conclusions
Reference
Suggested Reading
Section 4 Molecular and Biochemical Aspects of Organ Toxicology
19 Molecular Mechanisms of Respiratory Toxicity
19.1 Introduction
19.2 Anatomy and Function of the Respiratory Tract
19.3 Toxicant]Induced Lung Injury, Remodeling, and Repair
19.4 Occupational and Environmental Lung Diseases
Suggested
Reading
20 Molecular Mechanisms of Hepatotoxicity
20.1 Introduction
20.2 Liver Organization and Cellular Components
20.3 Acute and Chronic Hepatotoxicity
20.4 Types of Hepatotoxicity
20.5 Mechanisms of Hepatotoxicity
20.6 Autoprotection and Protective Priming
20.7 Experimental Prediction of Hepatotoxicity
20.8 Compounds Causing Liver Injury
20.9 Conclusions
Suggested
Reading
21 Molecular Mechanisms of Renal Toxicology
21.1 Introduction
21.2 Influence of Renal Structure and Function on Susceptibility to Nephrotoxicity and Renal Damage
21.3 Classification of Renal Injury
21.4 Assessment of Renal Function in the Clinic and in Animal Models
21.5 General Considerations for Choosing an Experimental Model to Study Nephrotoxicity
21.6 In Vitro Models to Study Mechanisms of Renal Injury
21.7 General Considerations Regarding Responses to Toxicants at the Cellular Level
21.8 Mechanisms of Toxicant Action in the Kidneys
21.9 Human Disease and Risk Assessment in Renal Toxicology
21.10 Summary
References
22 Molecular Mechanisms of Neurotoxicity
22.1 Introduction
22.2 Neurotransmission
22.3 Inter] and Intracellular Signaling
22.4 Excitotoxicity
22.5 Protein Modifications
22.6 Neuroinflammation
22.7 Epigenetics
22.8 Concluding Remarks
Suggested
Reading
23 Molecular Mechanisms of Immunotoxicity
23.1 Introduction and Overview of the Immune System
23.2 Immune Hypersensitivities and Autoimmune Disease
23.3 Mucosal Immunity, the Microbiome, and Food Allergies
23.4 Molecular Immunotoxicology of Environmental Stressors
23.5 Methods for Assessing Immunotoxicology
23.6 Summary
References
24 Molecular Mechanisms of Reproductive Toxicity
24.1 Introduction
24.2 Organization of the Reproductive System: Sexual Differentiation
24.3 Neuroendocrine Regulation of Reproduction
24.4 Female Reproductive System
24.5 Toxicity in the Male Reproductive System
24.6 Transgenerational Effects on Reproduction
24.7 Summary
References
25 Molecular Mechanisms of Developmental Toxicity
25.1 Introduction
25.2 Overview of Development and General Principles
25.3 Wilson’s Principles of Teratology
25.4 Selected Examples of Developmental Toxicants
25.5 Advances in Developmental Toxicology Methods
25.6 Summary
References
Section 5 Emerging Areas in Molecular and Biochemical Toxicology
26 Computational and Molecular Approaches to Risk Assessment
26.1 Introduction
26.2 High]Throughput Bioactivity
26.3 High]Throughput Toxicokinetics
26.4 High]Throughput Exposure
26.5 Summary
References
27 Nanotoxicology
27.1 Introduction
27.2 Naturally Occurring and Unintentional Nanoparticles
27.3 Engineered Nanomaterials
27.4 Exposure to Nanoparticles
27.5 Protein Corona Formation on Nanoparticles
27.6 Nanoparticle Interactions with Biological Barriers
27.7 Degradation and Clearance
27.8 Adverse Effects of Nanoparticles
27.9 Nanomedicine
27.10 Life Cycle of Nanoparticles in the Environment
Suggested Reading
28 Developmental Origins of Health and Disease
28.1 Introduction
28.2 Historical Perspective: Birth Weight and Early Life Nutrition in Adult Health
28.3 The Effects of Environmental Chemicals on the Programming of Adult Health
28.4 Biological Mechanisms
28.5 Conclusions
Suggested
Reading
29 Exposome
29.1 Introduction
29.2 The Exposome and Disease Pathways
29.3 The Blood Exposome
29.4 The Exposome and Social Factors
29.5 Discovering Causes of Disease
29.6 The Future of the Exposome

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