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Cellular Effects of Heavy Metals

✍ Scribed by Gaspar Banfalvi (editor)


Publisher
Springer
Year
2011
Tongue
English
Leaves
347
Category
Library

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✦ Synopsis


The term “heavy metals” is used as a group name of toxic metals and metalloids (semimetals) causing contaminations and ecotoxicity. In strict chemical sense the density of heavy metals is higher than 5 g/cm3. From biological point of view as microelements they can be divided into two major groups. a. For their physiological function organisms and cells require essential microelements such as iron, chromium (III), cobalt, copper, manganese, molidenium, zinc. b. The other group of heavy metals is toxic to the health or environment. Of highest concern are the emissions of As, Cd, Co, Cu, Hg, Mn, Ni, Pb, Sn, Tl. The toxicity of heavy metals is well known at organizational level, while less attention has been paid to their cellular effects. This book describes the toxicity of heavy metals on microorganisms, yeast, plant and animal cells. Other chapters of the book deal with their genotoxic, mutagenic and carcinogenic effects. The toxicity of several metals touch upon the aspects of environmental hazard, ecosystems and human health. Among the cellular responses of heavy metals irregularities in cellular mechanisms such as gene expression, protein folding, stress signaling pathways are among the most important ones. The final chapters deal with biosensors and removal of heavy metals. As everybody is eating, drinking and exposed to heavy metals on a daily basis, the spirit of the book will attract a wide audience.

✦ Table of Contents


Preface
Contents
Contributors
Abbreviations
Part I Introduction
Chapter 1
Heavy Metals, Trace Elements and Their Cellular Effects
Introduction
Why Another Book on Heavy Metals?
Brief Review of Chapters
Definition of Heavy Metals
Trace Metal Elements
Cellular Effects of Heavy Metals
Non-essential Harmful Heavy Metals
Cellular Toxicity of Heavy Metals
Detoxification of Heavy Metals
Detection of Cellular Toxicity of Heavy Metals
Replacing In Vivo Animal Studies with In Vitro Systems
Bacterial, Fungal and Mammalian In Vitro Systems
Mammalian Cell Cultures
Permeability Changes Caused by Heavy Metals
Oxidative Damages Caused by Heavy Metals
Lipid Peroxidation
Oxidative DNA Damage
Estimation of Toxic Effects of Heavy Metals
Tumorigenic Potential of Heavy Metals
Metabolic Parameters
Cytoskeletal and Nucleoskelatal Changes
Chromosomal and Chromatin Changes Induced by Heavy Metals
Detection of Apoptotic and Necrogenic Chromatin Changes
Detection and Determination of Heavy Metals in Cells
Spectroscopy, Spectrometry
Atomic Absorption Spectrophotometry
Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES)
X-ray Fluorescence
Backscatter Electron (BSE) Imaging and Energy Dispersive Spectroscopy
Amperometric Detection of Unithiol Complexes of Heavy Metals
Isotope Techniques
Isotope Dilution Mass Spectrometric Method (IDMS)
Tritium-Labelled Chelates
Whole-Cell-Sensing Systems
Protein Based Bisosensors
Construction of Metal Detection Circuits in E. coli
Luminescence-Based Whole-Cell-Sensing Systems using Genetically Engineered Bacteria
Whole-Cell Heavy Metal Detecting Yeast System using Cadmium-Inducible Gene Promoter
Heavy Metal Toxicity Detected by Cardiac Cell-Based Biosensor
Antibody-Based Sensors for Heavy Metal Ions
Porphyrin Test
Disposable Cuvette Test for the Enzymatic Determination of Heavy Metals
References
Part II Heavy Metal Toxicity in Microbes
Chapter 2
Toxic Metal/Metalloid Tolerance in Fungi—A Biotechnology-Oriented Approach
Introduction
First Line of Defense: Extracellular Chelation and Binding to Cell Wall Constituents
Second Line of Defense: Transport, Intracellular Chelation and Compartmentalization
Third Line of Defense: The Antioxidative Defense System
Screening for Future Targets to Engineer Heavy Metal Tolerant Fungi
References
Chapter 3
Interference of Chromium with Cellular Functions
Introduction
Chromium and Environment
Extracellular Reduction of Chromate
Metal Ion Uptake by Yeasts and Fungi
Biosorption of Chromium
Bioaccumulation of Chromium
Cellular Interactions of Chromium
Interactions of Chromium with Plasma Membrane
ROS Formation During Intracellular Cr(VI) Metabolism
Mechanisms of Chromium Sensitivity and Resistance
Interactions of Chromium with Biomolecules
Mechanism of Chromium Toxicity
Risk Assessment in Human Exposure to Cr(VI)
Inhalation
Dermal Absorption
Oral Intake
Kinetics and Metabolism
Excretion
Nutritional Practices and Assessment of Risk Involved in Human Exposure to Chromium(III)
Prevention and Repair of Chromium-Induced Damage
Conclusions
References
Chapter 4
Saccharomyces Cerevisiae as a Model Organism for Elucidating Arsenic Tolerance Mechanisms
Introduction
Impact of Arsenic on Yeast Cells
Arsenic Uptake Routes in Yeast
Arsenate Uptake
Arsenite Uptake
Arsenic Detoxification Systems in Yeast
ACR Gene Cluster—A Major Determinant of Arsenic Tolerance in Yeast
As(III)-responsive Transcription Factor Yap8p/Acr1p
Arsenate Reductase Acr2p
Arsenite Permease Acr3p
Role of Fps1p in As(III) Efflux
Vacuolar Sequestration of Metalloids
Glutathione Biosynthesis and the Role of Met4p
Oxidative Stress Defence and Yap1p
Hog1p and Cell Cycle Regulation in Response to As(III) Exposure
Other Detoxification and Tolerance Systems
Global Analysis of Tolerance Factors in Yeast
Proteasomal Degradation of Damaged Proteins
TOR- and PKA-Pathway: Regulation of General Stress Responses and Ribosomal Proteins
Yeast as a Model System for Elucidating the Molecular Biology of Arsenic Toxicity and Tolerance
Aquaporins, Metalloid Transport and Human Health
ACR-Proteins in Plants
Conclusions
References
Part III Heavy Metal Induced Toxicity in Insect Cells
Chapter 5
Heavy Metal Toxicity in an Insect Cell Line (Methyl-HgCl, HgCl2, CdCl2 and CuSO4)
Introduction
Materials
Cell Culture
Metal Exposure
Viability and Proliferation Assays
Light and Electron Microscopy
Atomic Absorption and Fluorescence Spectrometry
Biochemical Assays
Methods
Viability Assays
Growth Assays
Light Microscopy and Cytoskeleton Staining
Electron Microscopy
Autometallography
Atomic Absorption and Fluorescence Spectrometry
Biochemical Assays
Results and Discussion
Viability Tests
Proliferation Assays
General Cell Morphology (Light Microscopy)
Ultrastructural Effects (Electron Microscopy)
Metal Uptake
Mitochondrial Impairment and Anaerobic Metabolism in Cd-Treated Cells
Cadmium-Induced Molecular Defense Mechanisms
Conclusions
References
Part IV Genotoxic Effects of Heavy Metals
Chapter 6
Cellular Changes in Mammalian Cells Induced by Cadmium
Introduction
Oxydative DNA Damage Caused by Heavy Metals
Methods
Chemicals
Solutions
Cell Growth
Heavy Metal Treatment
Cell Cycle Synchronization
Flow Cytometry
Reversible Permeabilization of Cells
DNA Synthesis in Reversibly Permeabilized Cells
DNA Isolation
Random Oligonucleotide-Primed Synthesis (ROPS) Assay
Analysis of 8-hydroxy-2′-deoxyguanosine
Isolation of Nuclei
Spreads of Nuclear Structures
Visualization of Chromatin Structures
Results
Cellular Effects of Cadmium
Effect of Cd on Replicative and Repair Synthesis
DNA Strand Breaks and Oxidative DNA Damage Generated by Cd
Chromatin Changes Induced by Cd
Growth Inhibition by Cd in Murine PreB Cells
Chromatin Changes Induced by Cd in Murine PreB Cells
Discussion
References
Chapter 7
Chromatin Toxicity of Ni(II) Ions in K562 Erythroleukemia Cells
Introduction
Materials and Methods
Chemicals and Reagents
Cell Growth
Treatment with Nickel Chloride
Reversible Permeabilization of Cells
Isolation of Nuclei
Spreads of Nuclear Structures
Visualization of Large Scale Chromatin Structures
Time-Lapse Photography
Results
Cellular Toxicity of NiCl2
Chromatin Structures of Normal Untreated Cells
Density Changes in Chromatin Structures at Low (0.2 and 0.5 μM) Concentrations of Ni(II)
Apoptotic Chromatin Changes at Elevated (1–5 µM) Concentrations of Nickel Chloride
Chromatin Changes at Higher (10 µM) Nickel Chloride Concentration
Necrotic Chromatin Changes at High (50 µM) Nickel Chloride Concentration
Cellular Motion After 100 µM NiCl2 Treatment
Discussion
Conclusions
References
Chapter 8
Genotoxic Chromatin Changes in Schizosaccharomyces Pombe Induced by Hexavalent chromium (CrVI) Ions
Introduction
Materials and Methods
Materials and Solutions
Cell Growth
Toxicity of Cr (VI) on S. Pombe
Preparation of Protoplasts
Isolation and Visualization of Large Scale Chromatin Structures
Results
Visualization of Interphase Chromatin Structures of S. Pombe
Cellular Toxicity of Cr(VI)
Apoptotic Chromatin Changes at Low Cr(VI) Concentration (10–50 µM)
Necrotic Chromatin Changes at Higher Cr(VI) Concentration
Discussion
Conclusions
References
Chapter 9
Chromatin Changes upon Silver Nitrate Treatment in Human Keratinocyte HaCaT and K562 Erythroleukemia Cells
Introduction
Materials and Methods
Chemicals and Reagents
Cell Culture and Silver Nitrate Exposure
Isolation and Visualization of Large Scale Chromatin Structures
Time-Lapse Photography
Changes in Chromatin Structure upon Silver Nitrate Exposure
Results
Cell Viability After AgNO3 Treatment
Time-Lapse Analysis of Cell Death
Chromatin Structures in Control HaCaT Cells and After Subtoxic (0.5 µM) Concentration of Silver Nitrate Treatment
Chromatin Changes at Low (5–10 µM) Concentrations of Silver Nitrate in Nuclei of HaCaT Cells
Chromatin Changes at Elevated (15–20 µM) Concentrations of Silver Nitrate in Nuclei of HaCaT Cells
Chromatin Changes at Higher (30–50 µM) Concentrations of Silver Nitrate in Nuclei of HaCaT Cells
Chromatin Structures of Normal Untreated K562 Cells
Chromatin Changes at Low (0.5–5 µM) Concentrations of Silver Nitrate in Nuclei of K562 Cells
Shrinkage and Expansion of Nuclear Structures of K562 Cells at Elevated (10–50 µM) Ag+ Concentrations
Discussion
Biological Effects of Metallic Silver
Toxic Effects of Silver Ions
Cellular Effect of Silver Nitrate on Eukaryotic Cells
Conclusions
References
Part V Chemical Carcinogenesis Induced by Heavy Metals
Chapter 10
Heavy Metal-Induced Carcinogenicity: Depleted Uranium and Heavy-Metal Tungsten Alloy
Introduction
Depleted Uranium (DU)
Heavy-Metal Tungsten Alloy
Routes of Exposure
In Vitro Studies
Depleted Uranium
Heavy-Metal Tungsten Alloy
In Vivo Studies
Depleted Uranium
Heavy-Metal Tungsten Alloy
Human Exposures
Depleted Uranium
Heavy-Metal Tungsten Alloy
Conclusions
References
Chapter 11
Role of Oxidative Damage in Metal-Induced Carcinogenesis
Introduction
Basic Redox Biochemistry of Carcinogenic Metals
Oxidative DNA Damage
DNA Base Damage
Cross-Linking
Strand Scission
Depurination
Oxidative Protein Damage
Discussion
Conclusion
References
Part VI Cellular Responses to Heavy Metal Exposure
Chapter 12
Non-native Proteins as Newly-Identified Targets of Heavy Metals and Metalloids
Introduction
Principles of Protein Folding
Interaction of Heavy Metals with Functional Groups of Proteins
Interference of Heavy Metals with the Refolding of Chemically Denatured Proteins
Mechanism of Folding Inhibition by Heavy Metal Ions
Interference of As(III) Species with Oxidative Refolding of Disulfide Bond-Containing Proteins
Possible Sequels of Protein Folding Inhibition in Cells
Conclusions
References
Chapter 13
Cellular Mechanisms to Respond to Cadmium Exposure: Ubiquitin Ligases
Introduction
Ubiquitin System
E3 Ubiquitin Ligases
Cullin-Ring Ligases (CRLs)
The SCF-Complex
Cadmium and Ubiquitin Ligases
Cellular Response to Cadmium Exposure
Saccharomyces Cerevisiae Transcription Factor Met4
Cadmium Exposure Leads to the Disassembly of SCFMet30
The Schizosaccharomyces Pombe Transcription Factor Zip1
SCFPof1 is Responsible for the Ubiquitination of Zip1
Mammalian Transcription Factor Nrf2
KEAP1-CUL3 Ubiquitin Ligase is Responsible for the Ubiquitination of Nrf2
Conclusions
References
Chapter 14
Metals Induced Disruption of Ubiquitin Proteasome System, Activation of Stress Signaling and Apoptosis
Introduction
The Ubiquitin Proteasome System (UPS)
UPS and Neurodegenerative Disease
Environmental Metals Exposure and Neurodegenerative Disease
Results and Discussion
MeHg, Cd2+, and As3+ Induced Alteration of the Proteasome Activity
MeHg, Cd2+, and As3+ Induced Accumulation of HMW-polyUb
MeHg, Cd2+, and As3+ Induced Activation of MAPK Signaling
Integrative Genomic Gene Expression Analysis and Pathway Mapping
Interruptions of UPS Pathway
Conclusions
References
Part VII Biomarkers
Chapter 15
Blood Lead Level (BLL, B-Pb) in Human and Animal Populations: B-Pb as a Biological Marker to Environmental Lead Exposure
Introduction
Aims
Methods
Biomonitoring and Biomarkers: Human and Animal Approach
Toxicokinetics of Lead
Effects of Lead on Red Blood Cells
Biomarkers of Lead Exposure
Blood Lead Concentration
Blood Lead Levels’ Reference Values
Alternative Biomarkers
Lead in Plasma/Serum
Animal Populations
Biomonitoring in Pets
Conclusions
References
Part VIII Removal of Heavy Metals
Chapter 16
Removal of Heavy Metal Sulfides and Toxic Contaminants from Water
Introduction
Methods
Chemicals and Reagents
Precipitation and Removal of Heavy Metals
Determination of Heavy Metal Content
Fish
Guppy Ecotoxicity Test
Treatment with Carbogen Gas and Air Flow
Results
Analogy Between the Chemistry of Removing Cyanide and Heavy Metals
Removal of Hg2+, Ni2+ and Pb2+ as their Sulfides
Ecotoxicity Test of Heavy Metal Ions
Removal of Sodium Sulfide from Water
pH Changes during Carbogen Treatment
Survival of Fish upon Removal of Heavy Metal and Sodium Sulfide
Discussion
Conclusions
References
Index


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