An insight into new advances of current interest in metal toxicology, such as mechanisms important in risk-assessment for human health. The book also has chapters on emerging conceptual problems including resistance to metal toxicity effects on gene expression, alongside principles regarding drug-chelation of metals, the potential use of prophyrins as indicators of metal exposure and toxicity. The toxicology of specific metals of major public health concern are discussed in depth, such as mercury, aluminum, arsenic, chromium, and cadmium. Of interest to basic scientists as well as public health administrators.
Inhalt
1 Transplacental Transfer of Lead and Cadmium.- A. Introduction.- I. Comparison of Human and Rodent Fetal-Maternal Blood Barriers.- II. Methods for Sampling the Human Placenta.- B. Placental Transfer of Lead.- I. Mechanism of Placental Transfer of Lead.- II. Maternal Blood Lead Levels During Pregnancy.- III. Effect of Maternal Lead on Birth Outcomes.- IV. Effect of Lead on Neurobehavioral and Cognitive Development In Utero.- V. Mechanisms for the Neurotoxicity of Lead.- C. Placental Transfer of Cadmium.- I. Cadmium Levels in Human Placenta.- II. Cadmium Effects on Placenta and Fetus.- III. Interactions in Placenta Between Cadmium, Zinc and Copper, and Metallothionein.- D. Summary.- References.- 2 Porphyrin Metabolism as Indicator of Metal Exposure and Toxicity.- A. Introduction.- B. Heme Biosynthesis and Porphyrin Metabolism.- C. Mechanistic Basis of Metal-Induced Porphyria (Porphyrinuria).- I. Metal Effects on Specific Steps of the Heme Biosynthetic Pathway.- II. Metal-Induced Oxidation of Reduced Porphyrins.- D. Metal- and Metalloid-Induced Porphyrinopathies and Porphyrinurias.- I. Lead.- 1. Erythrocyte ALA Dehydratase.- 2. Erythrocyte Zinc-Protoporphyrin.- 3. Urinary Coproporphyrin.- II. Mercury.- 1. Mercury-Directed Alteration of Renal Coproporphyrinogen Metabolism.- 2. Mercury-Facilitated Porphyrinogen Oxidation.- III. Arsenic.- IV. Other Metals.- 1. Cadmium.- 2. Platinum.- 3. Aluminum.- 4. Metal Interactions.- E. Perspectives on the Use of Porphyrins as Biomarkers of Metal Exposure in Human Studies.- References.- 3 Membrane Transporters as Sites of Action and Routes of Entry for Toxic Metals.- A. Introduction: Metals and Membranes.- B. Chemical Properties of Metals in Solutions.- C. Model Systems.- D. Mercury Inhibition of NaCl Cotransport: An Example Problem with a Model System.- E. Metal Entry into Cells.- F. Permeation in a Lipid-Soluble Form.- G. Permeation as a Cation.- H. Permeation as an Anion.- I. Transport of Organic Complexes.- J. Physiological Significance of Metal Permeation Pathways.- References.- 4 Immunotoxicology of Metals.- A. Introduction.- B. Basis of the Immune Response.- C. Hypersensitivity Reactions.- D. Experimental Models of Metal-Induced Autoimmunity.- I. Description of the Models.- 1. HgCl2-Induced Autoimmunity in Rats.- 2. HgCl2-Induced Autoimmunity in Other Species.- 3. Gold-Induced Autoimmunity.- II. Mechanisms of Induction.- III. Autoregulation.- E. Nonantigen-Specific Immunosuppression Induced by HgCl2.- F. Conclusions.- References.- 5 Effects of Metals on Gene Expression.- A. Introduction.- B. Molecular Control of Gene Expression.- C. Eukaryotic Strategies of Signal Transfer.- I. Multiple Factor Signal Transduction Systems.- II. Single Factor Signal Transduction Systems.- D. Transduction of Metal Signals in Eukaryotes.- I. Entry, Binding, and Storage of Essential Metals.- 1. Iron.- 2. Copper.- II. Essential Metals as Regulators of Metabolism.- 1. Iron.- 2. Copper.- III. Metallothionein and Other Genes as Models for Metal Regulation.- 1. Metal Regulation in Yeast.- 2. Metal Regulation in Mammals.- IV. Metal Bioavailability and Sequestration.- E. Other Metal-Regulated Genes.- I. Plastocyanin and cyt c6.- II. Superoxide Dismutase.- III. Heat Shock Proteins.- IV. Acute Phase Proteins, Heme Oxygenase, and Oncogenes.- F. Metal-Induced Changes in Chromatin Structure.- G. Summary.- References.- 6 Metallothionein and Its Interaction with Metals.- A. Introduction.- B. Metal Binding and Dynamic Aspects of Metallothionein Structure.- C. Induction of Metallothionein and Excretion of Metals.- D. Detoxification of Metals.- E. Regulation of Zinc and Copper Metabolism.- F. Lipid Peroxidation and Oxidative Stress.- G. Summary.- References.- 7 Biochemical Mechanisms of Aluminum Toxicity.- A. Introduction.- B. Aluminum Species in Biological Systems.- C. Bioavailability of Aluminum.- I. Exposure.- II. Gastrointestinal Absorption.- III. Transcellular Uptake.- IV. Paracellular Uptake.- V. Systemic Transport.- VI. Accumulation in Erythrocytes.- VII. Cellular Uptake.- VIII. Aluminum Interactions with Desferrioxamine.- D. Aluminum-Related Anemia.- E. Aluminum-Related Bone Disease.- F. Aluminum Neurotoxicity.- G. Aluminum and Second Messenger Systems.- I. Fluoroaluminate Stimulation of G-Protein Systems.- II. Fluoride Stimulation of Second Messenger Systems.- III. Aluminum Stimulation of Second Messenger Systems.- IV. GTP Interaction with Aluminum.- References.- 8 Mercury Toxicity.- A. Introduction.- B. Organic Mercury.- I. Methylmercury.- 1. Mechanism of Uptake and Excretion.- 2. Mechanism of Toxicity.- C. Inorganic Mercury.- I. Mercuric Mercury.- 1. Tissue Accumulation and Excretion.- 2. Toxicity.- 3. Mechanism of Renal Toxicity.- II. Elemental Mercury.- 1. Exposure to Elemental Mercury.- 2. Metabolism.- 3. Biotransformation.- 4. Toxicity.- 5. Mechanism of Toxicity.- References.- 9 Toxicology of Cadmium.- A. Introduction.- I. Production and Uses.- II. Exposure to Cadmium.- III. Metabolism.- B. Molecular and Cellular Effects.- I. Calmodulin-Calcium-Cadmium Interactions.- II. Other Effects.- C. Target Organ Toxicity.- I. Acute Toxicities.- II. Chronic Toxicities.- 1. Lung.- 2. Kidney.- 3. Liver.- 4. Developmental Effects.- 5. Reproductive Effects.- 6. Bone.- 7. Immune Effects.- D. Carcinogenesis.- I. Human Studies.- II. Animal Studies.- 1. Lung.- 2. Prostate.- 3. Testes.- 4. Injection Site.- 5. Hematopoietic.- 6. Metal-Metal Interactions.- 7. Synergism and Antagonism.- E. Roles of Metallothionein and Glutathione in Cadmium Toxicity.- I. Metallothionein.- II. Glutathione.- F. Conclusion.- References.- 10 Chromium Toxicokinetics.- A. Introduction.- B. Chromium Actions and Kinetics.- I. Local and Systemic Toxicity.- II. Essentiality of Cr(III).- III. Carcinogenicity of Cr(VI).- C. Key Features of Chromium Kinetics.- I. Solubility.- II. Membrane Permeability and Chromium Absorption.- 1. Gastrointestinal Absorption.- 2. Pulmonary Absorption.- III. Reduction of Cr(VI) to Cr(III).- IV. General Chromium Disposition.- V. Chromium in the Red Cell.- VI. Chromium in Bone.- VII. Chromium in Other Tissues.- VIII. Excretion.- D. Uncertainties and Research Needs.- References.- 11 Metals and Stress Proteins.- A. Introduction.- B. Stress Proteins and Their Functions.- C. Metals and Their Effects on Expression of Stress Proteins.- I. General.- II. Arsenic.- III. Cadmium.- IV. Mercury.- V. Copper.- VI. Zinc.- VII. Lead.- VIII. Iron.- IX. Gold.- D. Tolerance Induction and Stress Proteins.- E. Heme Oxygenase Is a Stress Protein.- F. Is Metallothionein a Stress Protein?.- I. Evolutionary Conservation.- II. Common Inducers.- III. Protective Roles and Cross-tolerance.- IV. Gene Regulation.- V. Increased Expression in Neoplasms and Other Diseases.- VI. Adjuncts to Chemotherapy.- G. Stress Proteins as Biomarkers of Metal Exposure and Toxicity.- I. Rationale and Criteria.- II. Exposure and Toxicity.- III. Toxicity Screening Assays.- IV. Environmental Monitoring.- V. Human Applications.- References.- 12 Metals and Anticancer Drug Resistance.- A. Introduction.- B. Metal-Binding and Metal-Based Anticancer Agents.- I. Bleomycin.- II. Doxorubicin.- III. Cisplatin and Carboplatin.- C. Metal-Induced Anticancer Drug Resistance in Cell Culture.- I. Cadmium.- II. Zinc.- D. Metallothionein and Anticancer Drug Resistance.- I. In Vitro Metallothionein…