- Introduction
- Why Molecular Mechanisms?
- Toxicokinetics and Toxicodynamics
- Toxicokinetic Factors as Basic Mechanisms of Toxicity
- Toxicodynamic Factors as Basic Mechanisms of Toxicity
- Organ-Selective Toxicity
- Biological Basis of Organ-Selective Toxicity
- Molecular Homology
- Tissue-Selective Transcription Factors
- Tissue-Restricted Expression of Molecular Targets
- Selective Hepatotoxicity and Nephrotoxicity
- Xenobiotic-Bioactivating Enzymes
- Vectorial Transport of Xenobiotics
- Cellular Transport and Selective Accumulation
- Transmembrane Transport of Xenobiotics
- Cell-Specific Delivery of Xenobiotics to Intracellular Targets by Physiological Uptake Systems
- Multispecific Hepatic Bile Salt Uptake Systems
- Pulmonary Epithelial Cell Polyamine Carrier
- The Neuronal Dopamine Transporter and Xenobiotic-Induced Parkinsonism
- Xenobiotic Export Pumps
- Hepatobiliary Conjugate Export Pump and Cholestasis
- Multidrug Resistance in Cancer Cells
- Permeability of the Blood-Brain Barrier
- Bioactivation of Xenobiotics to Reactive Metabolites
- Biotransformation and Bioactivation/ -inactivation
- Phase I (Functionalization) and Phase II (Conjugation) Reactions
- Cyochrome P450 (CYP)
- Mechanisms and Toxicological Consequences of Isoform-Selective CYP Induction
- Mechanisms and Consequences of Isoform-Selective CYP Inhibition
- Bioactivation of Xenobiotics by CYP
- UDP-glucuronosyltransferase (UGT)
- Mechanisms and Toxicological Consequences of UGT Induction
- Reactive Acyl Glucuronides and Their Positional Isomers
- N-Glucuronidation of Aromatic Amines
- Sulfotransferase (SULT)
- N-Acetyltransferase (NAT)
- Bioactivation of Arylamines
- Toxicological Consequences of Individual NAT Expression
- Glutathione-S-Transferase (GST)
- Glutathione Conjugation as a Protective Mechanism
- Bioactivation of Xenobiotics by GST
- Mechanisms of Phototoxicity
- Protective Mechanisms against Reactive Metabolites: The Stress Response
- Induction of Heat Shock Proteins
- Targeting of Stress Response Proteins by Reactive Metabolites
- Xenobiotic-Induced Oxidative Stress: Cell Injury, Signaling, and Gene Regulation
- Reactive Oxygen Species (ROS) and Oxidoreductive Stress
- Mechanisms of Xenobiotic-Induced Intracellular ROS Production
- The Key Players: Superoxide Anion Radical, Hydrogen Peroxide, and Hydroxyl Radical
- Role of Iron and Other Redox-Active Transition Metals
- Mechanisms of Xenobiotic-Enhanced Extracellular ROS Production
- Other ROS: Ozone and Singlet Oxygen
- Reactive Nitrogen Species (RNS) and Oxidative Stress
- Toxicological Consequences of Oxidative Stress
- Oxidative DNA Damage
- Oxidative Protein Damage
- Oxidative Lipid Damage
- Interference with Antioxidant Defense Mechanisms
- Glutathione
- GSH-Coupled Enzyme Systems
- Genetic Deficiency in Erthrocyte Glucose-6-Phosphate Dehydrogenase
- Superoxide Dismutase
- Metallothionein
- α-Tocopherol
- Intracellular Signaling and Gene Regulation by Oxidative Stress
- Disruption of Cellular Calcium Homeostatsis
- Xenobiotic-Induced Alterations in Intracellular Ca2+ Distribution
- Toxicological Consequences of Increased Intracellular Ca2+ concentrations
- Mechanisms of Necrotic and Apoptotic Cell Death
- Mechanisms of Necrosis
- Apoptosis
- Molecular Mechanisms and Pathways of Apoptosis
- Signaling through Death Receptors
- Caspases – The Executors
- Role of Mitochondria
- Checkpoints – the Bcl-2 Proteins
- Suppression of Apoptosis – Toxicological Consequences
- Impairment of Cell Proliferation and Tissue Repair
- The Cell Cyle
- Stimulation of DNA synthesis and Cell Proliferation: Xenobiotics as Mitogens
- Inhibition of Cell Proliferation by Xenobiotics
- Inhibition of Tissue Repair
- Covalent Binding of Reactive Metabolites to Cellular Macromolecules
- Electrophiles and Nucleophilic Targets
- Covalent Protein Binding
- Selectivity of Covalent Adduct Formation
- Downstream Toxicological Consequences of Covalent Protein Binding
- Covalent Modification and Inactivation of Protein Phosphates
- Covalent Modification of Neurofilaments
- Covalent Modification of Proteins in the Biliary Tree and Small Intestine
- Covalent DNA Binding
- Toxicological Consequences of DNA Alkylation
- Immune Mechanisms
- Xenobiotic-Induced Activation of the Innate Immune System
- Immunosuppression by Xenobiotics
- Immune-Mediated Toxicity
- Autoimmune Reactions
- Immunoallergy
- Idiosyncratic Reactions and the “Danger”
- Cytokine-Mediated Toxicity
- Tumor Necrosis factor-α and other proinflammatory cytokines
- Chemokines and Inflammatory Cell Recruitment
- Specific Inactivation of Enzymes and Other Proteins
- Disruption of Acetylcholinesterase Activity
- Transthyretin Binding and Inactivation – Disruption of Thyroid Function
- Nuclear Receptor-Mediated Toxicity
- The Aryl Hydrocarbon Receptor (AHR)
- AHR-Mediated Toxicity of Polychlorinated Dibenzodioxins, Dibenzofurans, and Biphenyls
- Xenoextrogens and Anti-Androgens
- Estrogen Receptor (ER)-Mediated Toxicity
- Androgen Receptor (AR)-Mediated Toxicity
- Peroxisome Proliferator-Activated Receptors (PPARs)
- PPARα–Dependent Toxicity
- PPARy-Mediated Toxicity
- Interactions of Xenobiotics with Ion Transporters
- Interactions with Neuronal Na+ Channels
- Interactions with the Na+, K+-pump
- Disruption of Cellular Energy Production by Xenobiotics
- Mitochondrial Targets and Xenobiotic-Induced Bioenergy Crisis
- Protonophoretic and Uncoupling Activity of Xenobiotics
- Inhibition of NADH Production
- Inhibition of Mitochondrial Fatty Acyl –ßOxidation
- Xenobiotics as Pseudosubstrates for the Citrate Cycle
- Inhibition of the Electron Transport Chain and Increased Generation of ROS
- Opening of the Mitochondrial Membrane Permeability
- Outlook: From Mechanisms to Individual Expression of Genes
- Review Q&A
- Index
British Toxicology Society Newsletter
"Students taking formal training in toxicology would definitely benefit from adding this book to their collection, since it covers many recent advances in the field."
Toxicology Letters
"This recently-published volume is a clear state-of-the-art explanation and description of how chemicals disrupt biological targets on a molecular basis. It is a beauty!"
