Contents:

1. Molecular and Biochemical Toxicology: Definition and Scope --
1.1. Introduction / Robert C. Smart / Ernest Hodgson --
1.2. Sources of Information / Robert C. Smart / Ernest Hodgson --
1.3. Toxicology / Robert C. Smart / Ernest Hodgson --
1.4. Molecular and Cellular Toxicology / Robert C. Smart / Ernest Hodgson --
1.5. Proteomics and Metabolomics / Robert C. Smart / Ernest Hodgson --
1.6. Role of Molecular, Cellular, and Biochemical Toxicology: Implications for Risk Assessment / Robert C. Smart / Ernest Hodgson --
1.7. Conclusions / Robert C. Smart / Ernest Hodgson --
Suggested Reading / Robert C. Smart / Ernest Hodgson --
2. Molecular Techniques for the Study of Gene Function / Robert C. Smart / Ernest Hodgson --
2.1. Applicability of Molecular Techniques to Toxicology / Robert C. Smart / Yoshiaki Tsuji --
2.2. Overview of Genes, Chromatin, and Their Relationship / Robert C. Smart / Yoshiaki Tsuji. Note continued: 2.2.1. The Genetic Code and Flow of Genetic Information / Robert C. Smart / Yoshiaki Tsuji --
2.2.2. Chromatin and Gene Regulation / Robert C. Smart / Yoshiaki Tsuji --
2.3. Approaches to Characterize the Functions of Genes / Robert C. Smart / Yoshiaki Tsuji --
2.3.1. Molecular Cloning and Plasmid Vectors / Robert C. Smart / Yoshiaki Tsuji --
2.3.2. Construction of cDNA and Genomic Libraries / Robert C. Smart / Yoshiaki Tsuji --
2.3.3. Eukaryotic Expression Systems / Robert C. Smart / Yoshiaki Tsuji --
2.3.3.1. Gene Delivery into Mammalian Cells: Plasmid Vectors / Robert C. Smart / Yoshiaki Tsuji --
2.3.3.2. Inducible Expression Vector: The TET-Inducible System / Robert C. Smart / Yoshiaki Tsuji --
2.3.3.3. Gene Delivery into Mammalian Cells: Viral Vectors / Robert C. Smart / Yoshiaki Tsuji --
2.4. Gene Targeting Technologies / Robert C. Smart / Yoshiaki Tsuji. Note continued: 2.4.1. Gene Silencing by Knockdown with Small Interfering RNA (siRNA) / Robert C. Smart / Yoshiaki Tsuji --
2.4.2. Protein-Guided Gene Targeting: ZFN and TALEN / Robert C. Smart / Yoshiaki Tsuji --
2.4.3. RNA-Guided Gene Targeting: The CRISPR/CAS System / Robert C. Smart / Yoshiaki Tsuji --
2.5. Analysis of Gene Expression and Regulatory Mechanisms / Robert C. Smart / Yoshiaki Tsuji --
2.5.1. Southern and Northern Blot Analyses / Robert C. Smart / Yoshiaki Tsuji --
2.5.2. Western Blot Analysis / Robert C. Smart / Yoshiaki Tsuji --
2.5.3. Polymerase Chain Reaction (PCR) / Robert C. Smart / Yoshiaki Tsuji --
2.5.4. Reverse Transcription PCR (RT-PCR) and Real-Time PCR / Robert C. Smart / Yoshiaki Tsuji --
2.5.5. Promoter Deletion Analysis/Reporter Gene Assays / Robert C. Smart / Yoshiaki Tsuji --
2.5.6. Electrophoretic Mobility Shift Assay (EMSA) and Pulldown with Biotinylated Probe and Streptavidin Beads / Robert C. Smart / Yoshiaki Tsuji. Note continued: 2.5.7. Chromatin Immunoprecipitation (ChIP) and RNA Immunoprecipitation (RIP) / Robert C. Smart / Yoshiaki Tsuji --
2.5.8. Microarrays and RNA Sequencing / Robert C. Smart / Yoshiaki Tsuji --
2.6. Methods to Evaluate Gene Function in an Animal Model / Robert C. Smart / Yoshiaki Tsuji --
2.6.1. Procedure for Making Transgenic Mice Using Zygote Injection / Robert C. Smart / Yoshiaki Tsuji --
2.6.2. General Procedure for Making Knockout Mice Using Embryonic Stem Cells / Robert C. Smart / Yoshiaki Tsuji --
2.6.3. Making Conditional Knockout Mice Using the Cre/loxP Recombinant System / Robert C. Smart / Yoshiaki Tsuji --
2.6.4. Making Knockout Mice Using the CRISPR/CAS9 System / Robert C. Smart / Yoshiaki Tsuji --
References / Robert C. Smart / Yoshiaki Tsuji --
Suggested Reading / Robert C. Smart / Yoshiaki Tsuji --
3. Transcriptomics / Yoshiaki Tsuji / Robert C. Smart --
3.1. Introduction / B. Alex Merrick --
3.1.1. The Transcriptome / B. Alex Merrick. Note continued: 3.2. Cellular Organization and the Transcriptome / B. Alex Merrick --
3.2.1. Transcription / B. Alex Merrick --
3.2.2. Genes and Transcripts: Traits and Functions / B. Alex Merrick --
3.2.3. Annotation of the Transcriptome / B. Alex Merrick --
3.2.4. Annotation / B. Alex Merrick --
3.3. RNA Isolation / B. Alex Merrick --
3.3.1. Sample Collection for Transcriptome Analysis / B. Alex Merrick --
3.3.2. RNA Isolation Methods / B. Alex Merrick --
3.3.3. Quantitative and Qualitative RNA Measures / B. Alex Merrick --
3.4. Platforms for Transcriptome Analysis: Microarrays / B. Alex Merrick --
3.4.1. Microarray Platforms / B. Alex Merrick --
3.4.2. How Is Microarray Analysis Performed? / B. Alex Merrick --
3.4.3. Data Normalization / B. Alex Merrick --
3.4.4. Differential Expression and Data Analysis / B. Alex Merrick --
3.4.5. Genomes, Transcriptomes, and Microarrays / B. Alex Merrick --
3.4.6. Application of Microarrays to Toxicogenomics / B. Alex Merrick. Note continued: 3.5. RNA-seq: NextGen Sequencing of the Transcriptome / B. Alex Merrick --
3.5.1. Introduction / B. Alex Merrick --
3.5.2. DNA Sequencing / B. Alex Merrick --
3.5.3. RNA-seq / B. Alex Merrick --
3.5.4. Advantages and Disadvantages of RNA-seq / B. Alex Merrick --
3.5.5. RNA-seq Analysis / B. Alex Merrick --
3.5.6. Choosing RNA-seq or Microarray / B. Alex Merrick --
3.5.7. Application of RNA-seq to Chemical Toxicity / B. Alex Merrick --
3.6. Validation of Transcriptome Analysis / B. Alex Merrick --
3.7. Analysis of Gene Expression Data / B. Alex Merrick --
3.7.1. Introduction / B. Alex Merrick --
3.7.2. Hierarchical Clustering / B. Alex Merrick --
3.7.3. Principal Component Analysis (PCA) / B. Alex Merrick --
3.7.4. Biological Functional Analysis / B. Alex Merrick --
3.7.5. Pathway Analysis / B. Alex Merrick --
3.8. Summary / B. Alex Merrick --
References / B. Alex Merrick --
4. Proteomics / B. Alex Merrick --
4.1. Introduction to Proteomics / Michael S. Bereman. Note continued: 4.2. Mass Spectrometry / Michael S. Bereman --
4.2.1. Fundamentals of Mass Measurement / Michael S. Bereman --
4.2.2. Sample Preparation in Bottom-Up Proteomics / Michael S. Bereman --
4.2.3. Liquid Chromatography: An Essential Tool / Michael S. Bereman --
4.2.4. Ionization Methods / Michael S. Bereman --
4.2.5. Tandem Mass Spectrometry / Michael S. Bereman --
4.2.6. Bioinformatic Pipeline / Michael S. Bereman --
4.3. Quantitation of Proteins by LC-MS/MS / Michael S. Bereman --
4.3.1. Label-Free Quantitation / Michael S. Bereman --
4.3.2. Metabolic Labeling / Michael S. Bereman --
4.3.3. Isobaric Tags / Michael S. Bereman --
4.4. Emerging Research Areas in Proteomics / Michael S. Bereman --
4.4.1. Posttranslational Modifications / Michael S. Bereman --
4.4.2. Interactomics / Michael S. Bereman --
4.4.3. Toxicoproteomics / Michael S. Bereman --
4.5. Summary / Michael S. Bereman --
Suggested Reading / Michael S. Bereman --
5. Metabolomics / Michael S. Bereman. Note continued: 5.1. Introduction / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.2. Endogenous and Exogenous Metabolites / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.2.1. Endogenous Metabolites / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.2.2. Exogenous Metabolites / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.2.3. Exposome / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.3. Study Design and Experimental Considerations / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.3.1. Study Design Considerations / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell. Note continued: 5.3.2. Sample Collection, Storage, and Processing Considerations / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.4. Applications of Metabolomics / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.4.1. Behavior and Diagnosis / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.4.2. Drug Exposure and Adverse Outcomes / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.4.3. Chemical Exposure / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell / Susan C.J. Sumner / Wimal Pathmasiri --
5.4.4. Linking In Utero Exposure to Birth and Health Outcomes / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell. Note continued: 5.5. Technologies for Targeted and Broad-Spectrum Metabolomics / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.5.1. Nuclear Magnetic Resonance (NMR) Spectroscopy for Targeted and Broad-Spectrum Metabolomics / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.5.2. Mass Spectrometry for Targeted and Broad-Spectrum Metabolomics / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.5.2.1. Targeted Mass Spectrometry Metabolomics / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.5.2.2. Stable Isotope Resolved Metabolomics (SIRM) and Metabolic Flux Analysis / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell. Note continued: 5.5.2.3. Broad-Spectrum Mass Spectrometry Metabolomics / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.5.2.4. Coulometric Methods for Neurotransmitter Detection / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.6. Statistical and Multivariate Analysis and Pathway Mapping / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.6.1. Standard Statistical Approaches / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.6.2. Multivariate Analysis / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.6.3. Quality Control / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell. Note continued: 5.6.4. Mapping Metabolites to Biochemical Pathways / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell / Susan C.J. Sumner --
5.6.5. Modeling Approaches / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
5.7. Summary / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
Acknowledgment / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
References / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
6. Cellular Techniques / Susan C.J. Sumner / Wimal Pathmasiri / James E. Carlson / Susan L. McRitchie / Timothy R. Fennell --
6.1. Introduction / Sharon A. Meyer / Barbara A. Wetmore --
6.2. Cellular Studies in Intact Tissue / Sharon A. Meyer / Barbara A. Wetmore --
6.2.1. Whole Animal Studies / Sharon A. Meyer / Barbara A. Wetmore. Note continued: 6.2.2. Tissue Slices / Sharon A. Meyer / Barbara A. Wetmore --
6.3. Studies with Dispersed, Isolated Cells / Sharon A. Meyer / Barbara A. Wetmore --
6.3.1. Tissue Digestion and Cell Separation / Sharon A. Meyer / Barbara A. Wetmore --
6.3.2. Limited Maintenance in Defined Media / Sharon A. Meyer / Barbara A. Wetmore --
6.3.3. Long-Term Suspension Culture / Sharon A. Meyer / Barbara A. Wetmore --
6.4. Monolayer Cell Culture / Sharon A. Meyer / Barbara A. Wetmore --
6.4.1. Propagation of Primary and Passaged Cultures / Sharon A. Meyer / Barbara A. Wetmore --
6.4.2. Immortalized Cells / Sharon A. Meyer / Barbara A. Wetmore --
6.4.2.1. Cell Line Contamination / Sharon A. Meyer / Barbara A. Wetmore --
6.4.3. Modifications to Monolayer Cell Culture / Sharon A. Meyer / Barbara A. Wetmore --
6.4.3.1. Reconstructed/Bioengineered Tissue / Sharon A. Meyer / Barbara A. Wetmore --
6.4.4. Stem Cell Cultures / Sharon A. Meyer / Barbara A. Wetmore. Note continued: 6.5. Observation of Cultured Cells / Sharon A. Meyer / Barbara A. Wetmore --
6.6. Indicators of Toxicity / Sharon A. Meyer / Barbara A. Wetmore --
6.6.1. Intact Tissue / Barbara A. Wetmore / Sharon A. Meyer --
6.6.2. Cell Culture / Sharon A. Meyer / Barbara A. Wetmore --
6.6.3. High-Throughput Cellular Systems / Sharon A. Meyer / Barbara A. Wetmore --
6.7. Important Considerations and Advances / Sharon A. Meyer / Barbara A. Wetmore --
6.7.1. Considerations in In Vitro Cytotoxicity Assessments / Sharon A. Meyer / Barbara A. Wetmore --
6.7.2. Experimental Confounders to Interpretation of In Vitro Data / Sharon A. Meyer / Barbara A. Wetmore --
6.7.3. Relating In Vitro Effects to In Vivo Exposures / Sharon A. Meyer / Barbara A. Wetmore --
6.8. Replacement of Animal Testing with Cell Culture Models / Sharon A. Meyer / Barbara A. Wetmore --
6.9. Conclusion / Sharon A. Meyer / Barbara A. Wetmore --
Suggested Reading / Sharon A. Meyer / Barbara A. Wetmore. Note continued: Journals / Sharon A. Meyer / Barbara A. Wetmore --
7. Basic Concepts of Molecular Epidemiological Research Methods / Sharon A. Meyer / Barbara A. Wetmore --
7.1. Introduction / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.2. Molecular Epidemiology / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.2.1. Definition / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.2.2. Criteria for Biomarker Identification and Validation / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.2.3. Biomarker Development and Validation / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.2.3.1. Biomarker Development / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.2.3.2. Validity / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.2.3.3. Reliability / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.2.3.4. An Example / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle. Note continued: 7.3. Descriptive Epidemiologic Study Designs / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.3.1. Descriptive Epidemiology Is Used to Identify Patterns of Disease and Exposure / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.3.2. Disease and Death Occurrence Measurement / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.3.3. Example of Descriptive Study / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.4. Analytic Epidemiologic Studies / Randy L. Jirtle / Cathrine Hoyo / David A. Skaar --
7.4.1. Observational Studies / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.4.1.1. Cross-Sectional Studies / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.4.1.2. Case-Control Studies / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.4.1.3. Cohort Studies / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.5. Experimental Studies / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle. Note continued: 7.5.1. Analytic Approach / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.5.2. Experimental Study Example / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.6. Inferring Causality from Molecular Epidemiologic Data / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.6.1. Evidence of Statistical Associations and Apparent Dose-Response / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.6.1.1. Statistical Association / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.6.1.2. Random Error in Estimating the Magnitude of Associations / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.6.1.3. Dose-Response / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.6.1.4. Interaction or Effect Modification / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.6.1.5. Mediation / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.6.1.6. Confounding / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle. Note continued: 7.6.1.7. Information Bias / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.6.1.8. Selection Bias / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.6.1.9. Statistical Power / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.6.2. Temporal Sequence / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.6.2.1. An Example / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.6.3. Replicable Associations / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.6.3.1. An Example / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.6.4. Biological Plausibility of Associations Observed / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.6.4.1. An Example / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
7.7. Summary / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
References / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
Suggested Reading / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle. Note continued: Reading Materials Related to Examples / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
8. Phase I and Phase II Metabolism and Metabolic Interactions: A Summary / Cathrine Hoyo / David A. Skaar / Randy L. Jirtle --
8.1. Introduction / Ernest Hodgson --
8.2. Metabolic Enzymes / Ernest Hodgson --
8.3. Phase I Reactions / Ernest Hodgson --
8.3.1. Monooxygenases / Ernest Hodgson --
8.3.2. Non-Microsomal Oxidations / Ernest Hodgson --
8.3.3. Cooxidation by Cyclooxygenase / Ernest Hodgson --
8.3.4. Reduction Reactions / Ernest Hodgson --
8.3.5. Hydrolysis / Ernest Hodgson --
8.4. Phase II Reactions / Ernest Hodgson --
8.4.1. Glucuronide Conjugation / Ernest Hodgson --
8.4.2. Sulfate Conjugation / Ernest Hodgson --
8.4.3. Methyltransferases / Ernest Hodgson --
8.4.4. Glutathione S-Transferases (GSTs) and Mercapturic Acid Formation / Ernest Hodgson --
8.4.5. Acylation Reactions / Ernest Hodgson --
8.4.6. Amino Acid Conjugation / Ernest Hodgson. Note continued: 8.5. Reactive Metabolites / Ernest Hodgson --
8.6. Factors Affecting Metabolism / Ernest Hodgson --
8.6.1. Introduction / Ernest Hodgson --
8.6.2. Gender, Genetics, and Polymorphisms / Ernest Hodgson --
8.6.3. Inhibition and Induction / Ernest Hodgson --
8.6.3.1. Introduction / Ernest Hodgson --
8.6.3.2. Inhibition / Ernest Hodgson --
8.6.3.3. Induction / Ernest Hodgson --
8.7. Synergism and Potentiation / Ernest Hodgson --
8.8. Biphasic Effects / Ernest Hodgson --
8.9. Environmental Effects / Ernest Hodgson --
8.10. Human Variation in Toxicant Metabolism / Ernest Hodgson --
8.11. Summary of Toxicant Metabolism / Ernest Hodgson --
Suggested Reading / Ernest Hodgson --
9. Structure, Mechanism, and Regulation of Cytochromes P450 / Ernest Hodgson --
9.1. Introduction / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.2.Complexity of the Cytochrome 450 Gene Superfamily / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin. Note continued: 9.2.1. CYP Gene Families and Subfamilies / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.2.2. Pseudogenes and Alternate Splice Variants / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.3. Cytochrome P450 Structure / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.4. Mechanisms of P450 Catalysis / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.4.1. Catalytic Cycle / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.4.2. Catalytic Requirements / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.4.3. Substrate Specificity and Overlap / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.4.4. Endogenous Substrates / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.5. Cytochrome P450 Regulation / Matthew L. Edin / Darryl C. Zeldin / John M. Seubert --
9.5.1. Tissue Distribution / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin. Note continued: 9.5.2. Constitutive and Inducible P450 Enzymes / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.5.3. Aromatic Hydrocarbon Receptor Induction of P450s / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.5.4. Phenobarbital Induction of P450s / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.5.5. Induction of P450s by Peroxisome Proliferators / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.5.6. Hormonal Regulation of P450s / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.5.7. Nutritional Regulation of P450s / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.5.8. Regulation of P450s by Cytokines / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.5.9. Regulation of P450s by Nitric Oxide / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.6. Transgenic Animal Models / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin. Note continued: 9.7. Reactive Oxygen Species / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.8. Posttranslational Modification of P450s / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
9.9. Summary / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
Suggested Reading / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
10. Polymorphisms in Phase I and Phase II Genes and Outcomes / John M. Seubert / Matthew L. Edin / Darryl C. Zeldin --
10.1. Introduction / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson --
10.2. Toxicogenetics and Single Nucleotide Polymorphisms (SNPS) / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson --
10.3. Polymorphic Cytochrome P450 and Xenobiotics Metabolism / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson --
10.3.1. CYP2A6 / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson --
10.3.2. CYP2B6 / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson --
10.3.3. CYP2C9 / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson. Note continued: 10.3.4. CYP2C19 / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson --
10.3.5. CYP2D6 / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson --
10.3.6. Other CYP Polymorphisms and Outcomes / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson --
10.4. Other Polymorphic Phase I Genes and Xenobiotics Metabolism / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson --
10.4.1. Alcohol Dehydrogenase / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson --
10.4.2. Aldehyde Dehydrogenase / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson --
10.4.3. Flavin-Containing Monooxygenases / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson --
10.4.4. Epoxide Hydrolase / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson --
10.4.5. Serum Cholinesterase / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson --
10.4.6. Paraoxonase / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson --
10.5. Polymorphisms: Mechanistic Classification / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson. Note continued: 10.6. Methods for the Study of Polymorphisms / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson --
10.7. Phase II Gene Polymorphisms and Xenobiotics Metabolism / Edward L. Croom / Yoshiaki Tsuji / Ernest Hodgson --
10.7.1. UDP-Glucuronosyl Transferases (UGTs) / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson --
10.7.2. Glutathione Synthesis and Glutathione S-Transferases / Yoshiaki Tsuji / Edward L. Croom / Ernest Hodgson --
10.7.3.N-Acetyltransferases / Edward L. Croom / Ernest Hodgson / Yoshiaki Tsuji --
10.7.4. Sulfotransferases / Ernest Hodgson / Yoshiaki Tsuji / Edward L. Croom --
10.8. Regulation of Phase II Genes Via Antioxidant Responsive Element / Ernest Hodgson / Edward L. Croom / Yoshiaki Tsuji --
Suggested Reading / Yoshiaki Tsuji / Ernest Hodgson / Edward L. Croom --
11. Cellular Transport and Elimination / Edward L. Croom / Ernest Hodgson / Yoshiaki Tsuji. Note continued: 11.1. Transport as a Determinant of Xenobiotic Action / David S. Miller / Ronald E. Cannon --
11.2. Factors Affecting Membrane/Tissue Permeability / David S. Miller / Ronald E. Cannon --
11.2.1. Cellular Level Transport / Ronald E. Cannon / David S. Miller --
11.2.2. Tissue Level Transport / David S. Miller / Ronald E. Cannon --
11.3. Xenobiotic Transporters / David S. Miller / Ronald E. Cannon --
11.3.1. Transporter Families / David S. Miller / Ronald E. Cannon --
11.3.1.1. ABC Transporters / David S. Miller / Ronald E. Cannon --
11.3.1.2.Organic Anion Transporters (OATs; SLC22A) / Ronald E. Cannon / David S. Miller --
11.3.1.3.Organic Cation Transporters (OCTs; SLC22A) / Ronald E. Cannon / David S. Miller --
11.3.1.4.Organic Anion Transporters (OATPs) / Ronald E. Cannon / David S. Miller --
11.3.1.5. Nucleoside and Nucleotide Transporters (SLC28 and SLC29) / David S. Miller / Ronald E. Cannon. Note continued: 11.3.1.6. Peptide Transporters (SLC15) / Ronald E. Cannon / David S. Miller --
11.3.2. Determining the Molecular Basis for Transport in Cells and Tissues / Ronald E. Cannon / David S. Miller --
11.4. Altered Xenobiotic Transport / David S. Miller / Ronald E. Cannon --
11.4.1.Competition for Transport / David S. Miller / Ronald E. Cannon --
11.4.2. Specific Regulation / David S. Miller / Ronald E. Cannon --
11.4.2.1. Transporter Expression / David S. Miller / Ronald E. Cannon --
11.4.2.2. Transporter Function / David S. Miller / Ronald E. Cannon --
11.4.3. Genetic Heterogeneity / David S. Miller / Ronald E. Cannon --
Suggested Reading / David S. Miller / Ronald E. Cannon --
12. Nuclear Receptors / David S. Miller / Ronald E. Cannon --
12.1. Introduction / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc --
12.2. NR Structure Function / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc. Note continued: 12.3. Nomenclature / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc --
12.4. NR Transactivation / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc --
12.4.1. DNA Binding / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc --
12.4.2. RXR Heterodimerization / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc --
12.4.3. Coregulators / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc --
12.5. NRS in Toxicology / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc --
12.5.1. Endocrine Disruption / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc --
12.5.2. Estrogen Receptor (ER) / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc --
12.5.3. Retinoid X Receptor (RXR) / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc --
12.5.4. Thyroid Hormone Disruption (TR) / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc. Note continued: 12.5.5. Peroxisome Proliferator-Activated Receptors (PPARs) / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc --
12.6. Endobiotic and Xenobiotic Metabolism / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc --
12.6.1. Pregnane X Receptor/Constitutive Androstane Receptor (PXR, CAR) / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc --
12.6.2. FXR/LXR Bile Acid and Cholesterol Homeostasis / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc --
12.7. Defining New NR Targets for Toxicity: Toxcast and Tox21 / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc --
Reference / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc --
Suggested Reading / Gerald A. LeBlanc / Seth W. Kullman / William S. Baldwin --
13. Mechanisms of Cell Death / Seth W. Kullman / William S. Baldwin / Gerald A. LeBlanc --
13.1. Introduction / Mac Law / Susan Elmore --
13.2. How Cells/Tissues React to "Stress" / Mac Law / Susan Elmore. Note continued: 13.2.1. Levels of Adaptation: Physiology Versus Pathology / Mac Law / Susan Elmore --
13.2.2. Hypertrophy / Mac Law / Susan Elmore --
13.2.3. Hyperplasia / Mac Law / Susan Elmore --
13.2.4. Atrophy / Mac Law / Susan Elmore --
13.2.5. Metaplasia / Mac Law / Susan Elmore --
13.2.6. Dysplasia / Mac Law / Susan Elmore --
13.3. Cell Injury and Cell Death / Mac Law / Susan Elmore --
13.3.1. Causes of Cell Injury and Cell Death / Mac Law / Susan Elmore --
13.3.1.1. Hypoxia / Mac Law / Susan Elmore --
13.3.1.2. Physical Agents / Mac Law / Susan Elmore --
13.3.1.3. Chemicals / Mac Law / Susan Elmore --
13.3.1.4. Microbial Agents / Mac Law / Susan Elmore --
13.3.1.5. Other Causes / Mac Law / Susan Elmore --
13.3.2. Pathogenesis of Reversible Versus Irreversible Cell Injury / Mac Law / Susan Elmore --
13.3.2.1. Irreversible Injury / Mac Law / Susan Elmore --
13.3.2.2. Leakage Enzymes Correlate with Cell Injury / Mac Law / Susan Elmore. Note continued: 13.3.3. Mechanisms of Irreversibility in Cell Injury / Mac Law / Susan Elmore --
13.4. Morphology of Cell Injury and Cell Death / Mac Law / Susan Elmore --
13.4.1. Cell Swelling (Hydropic Degeneration) / Mac Law / Susan Elmore --
13.4.2. Types of Necrosis / Mac Law / Susan Elmore --
13.4.2.1. Coagulative Necrosis / Mac Law / Susan Elmore --
13.4.2.2. Caseous Necrosis / Mac Law / Susan Elmore --
13.4.2.3. Fat Necrosis / Mac Law / Susan Elmore --
13.4.2.4. Liquefactive Necrosis / Mac Law / Susan Elmore --
13.4.3. Microscopic Appearance of Necrosis / Mac Law / Susan Elmore --
13.5. Apoptosis, Morphology, and Mechanisms / Mac Law / Susan Elmore --
13.5.1. Morphology of Apoptosis / Mac Law / Susan Elmore --
13.5.2. Mechanisms of Apoptosis / Mac Law / Susan Elmore --
13.5.2.1. Biochemical Features / Mac Law / Susan Elmore --
13.5.2.2. Extrinsic Pathway / Mac Law / Susan Elmore --
13.5.2.3. Perforin/Granzyme Pathway / Mac Law / Susan Elmore. Note continued: 13.5.2.4. Intrinsic Pathway / Mac Law / Susan Elmore --
13.5.2.5. Execution Pathway / Mac Law / Susan Elmore --
13.5.3. Physiologic Apoptosis / Mac Law / Susan Elmore --
13.5.4. Pathologic Apoptosis / Mac Law / Susan Elmore --
13.5.5. Inhibition of Apoptosis / Mac Law / Susan Elmore --
13.5.6. Assays for Apoptosis / Mac Law / Susan Elmore --
13.5.6.1. Cytomorphological Alterations / Mac Law / Susan Elmore --
13.5.6.2. DNA Fragmentation / Mac Law / Susan Elmore --
13.5.6.3. Detection of Caspases, Cleaved Substrates, Regulators, and Inhibitors / Mac Law / Susan Elmore --
13.5.6.4. Membrane Alterations / Mac Law / Susan Elmore --
13.5.6.5. Detection of Apoptosis in Whole Mounts / Mac Law / Susan Elmore --
13.5.6.6. Mitochondrial Assays / Mac Law / Susan Elmore --
13.6. Other Cell Death Modalities / Mac Law / Susan Elmore --
13.6.1. Autophagy / Mac Law / Susan Elmore --
13.6.2. Necroptosis / Mac Law / Susan Elmore --
13.6.3. Pyroptosis / Mac Law / Susan Elmore. Note continued: 13.6.4. Eryptosis / Mac Law / Susan Elmore --
13.6.5. Anoikis / Mac Law / Susan Elmore --
Acknowledgments / Mac Law / Susan Elmore --
Reference / Mac Law / Susan Elmore --
Suggested Reading / Mac Law / Susan Elmore --
14. Mitochondria! Dysfunction / Mac Law / Susan Elmore --
14.1. Introduction / Jun Ninomiya-Tsuji --
14.2. Mitochondrial Function / Jun Ninomiya-Tsuji --
14.2.1. Structure: Outer and Inner Membranes / Jun Ninomiya-Tsuji --
14.2.2. Generating High-Energy Electrons (TCA Cycle, Fatty Acid Oxidation, FADH2, and NADH) / Jun Ninomiya-Tsuji --
14.2.3. Respiratory Chain (Complexes I, II, III, and IV and Ubiquinone, Cytochrome c, Proton Pump, Membrane Potential, Proton Motive Force) / Jun Ninomiya-Tsuji --
14.2.3.1. Step 1: Complex I / Jun Ninomiya-Tsuji --
14.2.3.2. Step 1': Complex II / Jun Ninomiya-Tsuji --
14.2.3.3. Step 2: Complex III / Jun Ninomiya-Tsuji --
14.2.3.4. Step 3: Complex IV / Jun Ninomiya-Tsuji. Note continued: 14.2.3.5. Step 4: ATP Synthase / Jun Ninomiya-Tsuji --
14.2.4. Mitochondrial Membrane Pore Complex (VDAC, ANT) / Jun Ninomiya-Tsuji --
14.2.5. Dynamic Organelle: Mitochondria (Fusion and Fission) / Jun Ninomiya-Tsuji --
14.3. Mitochondrial Apoptosis/Necrosis / Jun Ninomiya-Tsuji --
14.3.1. Mitochondrial Membrane Permeabilization / Jun Ninomiya-Tsuji --
14.3.2. Caspase Activation: Effector and Initiator Caspases / Jun Ninomiya-Tsuji --
14.3.3. Mitochondria Are "Pandora's Box" / Jun Ninomiya-Tsuji --
14.3.4. Interplay of Bc12 Family (BH3-only, Bc12, Bax/Bak) / Jun Ninomiya-Tsuji --
14.3.5. Inner-Membrane Permeabilization / Jun Ninomiya-Tsuji --
14.3.6. Cross Talk Between Bax/Bak and Inner-Membrane Permeabilization / Jun Ninomiya-Tsuji --
14.4. Toxicant-Induced Mitochondrial Apoptosis/Necrosis / Jun Ninomiya-Tsuji --
14.4.1. Electron Transport Inhibitors / Jun Ninomiya-Tsuji --
14.4.2. Energy Transfer Inhibitors / Jun Ninomiya-Tsuji. Note continued: 14.4.3. Uncouplers / Jun Ninomiya-Tsuji --
References / Jun Ninomiya-Tsuji --
15. Reactive Metabolites, Reactive Oxygen Species (ROS), and Toxicity / Jun Ninomiya-Tsuji --
15.1. Introduction / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.2. Enzymes Involved in Bioactivation / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.2.1. Phase I Oxidations / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.2.1.1. Cytochrome P450 / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.2.1.2. Flavin-Containing Monooxygenase / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.2.1.3. Prostaglandin Synthetase / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.2.2. Phase II Conjugations / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.2.3. Intestinal Microflora / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.3. Stability of Reactive Metabolites / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.4. Factors Affecting Metabolic Balance and Toxicity / Elizabeth L. MacKenzie / Yoshiaki Tsuji. Note continued: 15.4.1. Saturation of Detoxication Pathways / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.4.2. Enzyme Induction / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.4.3. Genetic and Physiological Factors / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.4.4. Metabolic Interactions / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.4.5. DNA Adduct Formation / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.4.6. Redox Cycling / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.5. Reactive Oxygen Species (ROS) and Toxicity / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.5.1. Generation and Detoxication of ROS / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.5.2. Measurement of ROS / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.5.3. Oxidative DNA Damage / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.5.4. Protein Oxidation / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
15.5.5. Lipid Peroxidation / Elizabeth L. MacKenzie / Yoshiaki Tsuji. Note continued: 15.5.6. ROS and Human Diseases / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
Suggested Reading / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
16. DNA Damage and Mutagenesis / Elizabeth L. MacKenzie / Yoshiaki Tsuji --
16.1. Introduction / Zhigang Wang --
16.2. Endogenous DNA Damage / Zhigang Wang --
16.2.1. DNA Base Mismatches / Zhigang Wang --
16.2.2. Base Deamination / Zhigang Wang --
16.2.3. AP Site / Zhigang Wang --
16.2.4. Oxidative DNA Damage / Zhigang Wang --
16.2.5. DNA Adducts Formed from Lipid Peroxidation Products / Zhigang Wang --
16.2.6. DNA Methylation / Zhigang Wang --
16.2.7. Incorporation of Inappropriate and Damaged dNTP into DNA during Replication / Zhigang Wang --
16.2.7.1. Incorporation of Uracil into DNA / Zhigang Wang --
16.2.7.2. Genomic DNA of the Bacillus subtilis Phage PBS2 Naturally Contains Uracil instead of Thymine / Zhigang Wang --
16.2.7.3. Incorporation of 8-Oxoguanine into DNA / Zhigang Wang. Note continued: 16.3. Environmental DNA Damage / Zhigang Wang --
16.3.1. DNA Damage by Ionizing Radiation / Zhigang Wang --
16.3.1.1. Base Damage and Single-Strand Breaks / Zhigang Wang --
16.3.1.2. Multiply Damaged Sites and Double-Strand Breaks / Zhigang Wang --
16.3.2. DNA Damage by UV Radiation / Zhigang Wang --
16.3.2.1. The Major UV Lesions: Cyclobutane Pyrimidine Dimers and (6-4) Photoproducts / Zhigang Wang --
16.3.2.2. Minor DNA Lesions of UV Radiation / Zhigang Wang --
16.3.3. DNA Damage by Chemicals / Zhigang Wang --
16.3.3.1. DNA-Damaging Chemicals Without Metabolic Activation / Zhigang Wang --
16.3.3.2. DNA-Damaging Chemicals That Require Metabolic Activation / Zhigang Wang --
16.3.4. Nanoparticles and DNA Damage / Zhigang Wang --
16.4. Concepts of Mutagenesis / Zhigang Wang --
16.4.1. Definition of Terms / Zhigang Wang --
16.4.1.1. General Terms / Zhigang Wang --
16.4.1.2. Terms Based on Phenotypic Consequences / Zhigang Wang. Note continued: 16.4.1.3. Terms Based on DNA Sequence Changes / Zhigang Wang --
16.4.2. Origin of Mutagenesis / Zhigang Wang --
16.4.3. Biological Significance of Mutagenesis / Zhigang Wang --
16.5. Mechanisms of DNA Damage-Induced Mutagenesis / Zhigang Wang --
16.5.1. Chromosomal Aberrations / Zhigang Wang --
16.5.2. Mutagenesis Induced by DNA Double-Strand Breaks / Zhigang Wang --
16.5.3. Mutagenesis Induced by DNA Base Damage / Zhigang Wang --
16.5.3.1. The Major Mechanism of Base Damage-Induced Mutagenesis Is Error-Prone Translesion Synthesis / Zhigang Wang --
16.5.3.2. Mechanistic Models of Translesion Synthesis / Zhigang Wang --
16.5.3.3. The Y Family of DNA Polymerases / Zhigang Wang --
16.5.3.4. Properties of the Y-Family DNA Polymerases / Zhigang Wang --
16.5.3.5. Polk Is a Major Extension Polymerase for Translesion Synthesis / Zhigang Wang --
16.5.3.6. Translesion Synthesis Is Part of the DNA Damage Tolerance System / Zhigang Wang. Note continued: 16.5.3.7. Control of Translesion Synthesis and Mutagenesis / Zhigang Wang --
16.5.3.8. The Y-Family DNA Polymerases Contain Sequence Motifs for Protein-Protein Interactions / Zhigang Wang --
16.5.3.9. Translesion Synthesis Is a Complex Pathway / Zhigang Wang --
16.5.3.10. Translesion Synthesis: Determining Error-Free Versus Error-Prone / Zhigang Wang --
16.5.4. Mutagenic Signatures of Selected DNA Lesions / Zhigang Wang --
16.5.4.1. AP Sites / Zhigang Wang --
16.5.4.2. UV Photoproducts / Zhigang Wang --
16.5.4.3. BPDE-N2-dG Adducts / Zhigang Wang --
16.5.4.4. The 1,N6-Ethenoadenine Adducts / Zhigang Wang --
16.5.4.5. Cisplatin / Zhigang Wang --
16.5.5. Damage-Induced Mutagenesis in Immunology: Somatic Hypermutation / Zhigang Wang --
Suggested Reading / Zhigang Wang --
17. DNA Repair / Zhigang Wang --
17.1. Introduction / Isabel Mellon --
17.2. Direct Reversal of Base Damage / Isabel Mellon --
17.2.1. UV Radiation / Isabel Mellon. Note continued: 17.2.2. Alkylation Damage / Isabel Mellon --
17.3. Base Excision Repair / Isabel Mellon --
17.3.1. Glycosylases / Isabel Mellon --
17.3.1.1. Uracil / Isabel Mellon --
17.3.1.2. Alkylated Bases / Isabel Mellon --
17.3.1.3. Oxidized and Fragmented Bases / Isabel Mellon --
17.3.1.4. Pyrimidine Dimers / Isabel Mellon --
17.3.2. AP Endonucleases / Isabel Mellon --
17.3.3. Repair Synthesis and Ligation / Isabel Mellon --
17.3.4. Base Excision Repair and DNA Methylation / Isabel Mellon --
17.4. Nucleotide Excision Repair SOS / Isabel Mellon --
17.4.1. DNA Damage Recognition / Isabel Mellon --
17.4.2.E. coli / Isabel Mellon --
17.4.3. Mammalian Cells / Isabel Mellon --
17.4.4. Nucleotide Excision Repair and Transcription / Isabel Mellon --
17.4.5. Human Diseases / Isabel Mellon --
17.5. Mismatch Repair / Isabel Mellon --
17.5.1.E. coli / Isabel Mellon --
17.5.2. Mammalian Cells / Isabel Mellon --
17.5.3. Cancer / Isabel Mellon --
17.6. Recombinational Repair / Isabel Mellon. Note continued: 17.6.1. Double-Strand Break Repair in E. coli / Isabel Mellon --
17.6.2. Double-Strand Break Repair in Eukaryotic Cells / Isabel Mellon --
17.6.3. Interstrand Cross-Link Repair / Isabel Mellon --
17.7. DNA Repair and Chromatin Structure / Isabel Mellon --
17.7.1. Chromatin Structure / Isabel Mellon --
17.7.2. Chromatin Remodeling in DNA Repair / Isabel Mellon --
17.8. DNA Repair in Mitochondria / Isabel Mellon --
17.9. DNA Repair and Cancer / Isabel Mellon --
17.10. Summary / Isabel Mellon --
Reference / Isabel Mellon --
Suggested Reading / Isabel Mellon --
18. Carcinogenesis / Isabel Mellon --
18.1. Introduction / Robert C. Smart / Jonathan R. Hall --
18.2. Human Cancer / Robert C. Smart / Jonathan R. Hall --
18.2.1. Hallmarks of Cancer / Robert C. Smart / Jonathan R. Hall --
18.2.2. Cancer Nomenclature / Robert C. Smart / Jonathan R. Hall --
18.2.3. Causes, Incidence, and Mortality Rates / Robert C. Smart / Jonathan R. Hall. Note continued: 18.2.4. Classification of Carcinogens / Robert C. Smart / Jonathan R. Hall --
18.3. Categorization of Agents Associated with Carcinogenesis / Jonathan R. Hall / Robert C. Smart --
18.3.1. DNA-Damaging Agents / Jonathan R. Hall / Robert C. Smart --
18.3.2. Nongenotoxic Agents / Jonathan R. Hall / Robert C. Smart --
18.4. Somatic Mutation Theory / Jonathan R. Hall / Robert C. Smart --
18.4.1. Electrophilic Theory, Metabolic Activation, and DNA Adducts / Jonathan R. Hall / Robert C. Smart --
18.4.2. DNA Damage / Jonathan R. Hall / Robert C. Smart --
18.4.3.Complete Carcinogenesis Model / Jonathan R. Hall / Robert C. Smart --
18.5. Epigenetic Mechanism of Tumorigenesis / Jonathan R. Hall / Robert C. Smart --
18.6. Multistage Tumorigenesis / Jonathan R. Hall / Robert C. Smart --
18.6.1. Initiation-Promotion Model / Jonathan R. Hall / Robert C. Smart --
18.6.2. Mechanisms of Tumor Promotion / Jonathan R. Hall / Robert C. Smart. Note continued: 18.7. Oncogenes / Jonathan R. Hall / Robert C. Smart --
18.7.1. Cell Transformation: Role of Carcinogens and Oncogenes / Jonathan R. Hall / Robert C. Smart --
18.7.2. Activation of Proto-Oncogenes to Oncogenes / Jonathan R. Hall / Robert C. Smart --
18.7.3. Oncogenes and Signal Transduction / Jonathan R. Hall / Robert C. Smart --
18.7.4. Oncogene Classification / Jonathan R. Hall / Robert C. Smart --
18.7.4.1. Growth Factors as Oncogenes / Jonathan R. Hall / Robert C. Smart --
18.7.4.2. Receptor Tyrosine Kinases as Oncogenes / Jonathan R. Hall / Robert C. Smart --
18.7.4.3. Non-Receptor Tyrosine Kinases as Oncogenes / Jonathan R. Hall / Robert C. Smart --
18.7.4.4. Small Guanosine Triphosphatases as Oncogenes / Jonathan R. Hall / Robert C. Smart --
18.7.4.5. Serine/Threonine Kinases as Oncogenes / Jonathan R. Hall / Robert C. Smart --
18.7.4.6. Transcription Factors as Oncogenes / Jonathan R. Hall / Robert C. Smart. Note continued: 18.7.4.7. Oncogenic Proteins Involved in Cell Survival / Jonathan R. Hall / Robert C. Smart --
18.7.5. Oncogene Cooperation / Jonathan R. Hall / Robert C. Smart --
18.8. Tumor Suppressor Genes / Jonathan R. Hall / Robert C. Smart --
18.8.1. Retinoblastoma Gene and the Cell Cycle / Jonathan R. Hall / Robert C. Smart --
18.8.2. Cyclin-Dependent Kinase Inhibitors and the pRB Circuit / Jonathan R. Hall / Robert C. Smart --
18.8.3.pRB Is Inactivated in Tumorigenesis by Multiple Mechanisms / Jonathan R. Hall / Robert C. Smart --
18.8.4.p53 / Jonathan R. Hall / Robert C. Smart --
18.8.5.p14ARF / Jonathan R. Hall / Robert C. Smart --
18.9. Mutator Phenotype/DNA Stability Genes / Jonathan R. Hall / Robert C. Smart --
18.10. Conclusions / Jonathan R. Hall / Robert C. Smart --
Reference / Jonathan R. Hall / Robert C. Smart --
Suggested Reading / Jonathan R. Hall / Robert C. Smart --
19. Molecular Mechanisms of Respiratory Toxicity / Jonathan R. Hall / Robert C. Smart.