Mechanistic toxicology: the molecular basis of how chemicals disrupt biological targets
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| Main Author: | |
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| Format: | Book |
| Language: | English |
| Published: |
Boca Raton
CRC Press
2009
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| Edition: | 2. ed. |
| Subjects: | |
| Online Access: | Publisher description Inhaltsverzeichnis |
| Item Description: | Includes bibliographical references and index |
| Physical Description: | 399 S. Ill., graph. Darst. cm |
| ISBN: | 0849372720 9780849372728 |
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MARC
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| 100 | 1 | |a Boelsterli, Urs A. |e Verfasser |4 aut | |
| 245 | 1 | 0 | |a Mechanistic toxicology |b the molecular basis of how chemicals disrupt biological targets |c Urs A. Boelsterli |
| 250 | |a 2. ed. | ||
| 264 | 1 | |a Boca Raton |b CRC Press |c 2009 | |
| 300 | |a 399 S. |b Ill., graph. Darst. |c cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 500 | |a Includes bibliographical references and index | ||
| 650 | 7 | |a Biologia molecular |2 larpcal | |
| 650 | 7 | |a Toxicologia |2 larpcal | |
| 650 | 4 | |a Toxicologie moléculaire | |
| 650 | 7 | |a Transdução de sinal celular |2 larpcal | |
| 650 | 4 | |a Molecular toxicology | |
| 650 | 4 | |a Toxicology |x methods | |
| 650 | 4 | |a Molecular Biology |x methods | |
| 650 | 4 | |a Signal Transduction | |
| 650 | 4 | |a Xenobiotics |x pharmacokinetics | |
| 650 | 4 | |a Xenobiotics |x toxicity | |
| 856 | 4 | |u http://www.loc.gov/catdir/enhancements/fy0703/2006035219-d.html |3 Publisher description | |
| 856 | 4 | 2 | |m GBV Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016075542&sequence=000005&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-016075542 | ||
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| _version_ | 1804137129078423552 |
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| adam_text | SECOND EDITION MECHANISTIC TOXICOLOGY THE MOLECULAR BASIS OF HOW
CHEMICALS DISRUPT BIOLOGICAL TARGETS URS A. BOELSTERLI CRC PRESS TAVLOR
& FRANCE CROUP CRC PRESS IS AN IMP^T O* :H TAYLOR H FRANCN C R,,JP I A
. CONTENTS CHAPTER 1 INTRODUCTION 1 1.1 WHY MOLECULAR MECHANISMS? 1 1.2
TOXICOKINETICS AND TOXICODYNAMICS 5 1.2.1 TOXICOKINETIC FACTORS AS BASIC
MECHANISMS OF TOXICITY 6 1.2.2 TOXICODYNAMIC FACTORS AS BASIC MECHANISMS
OF TOXICITY 7 LEARNING POINTS 12 FURTHER READING 13 CHAPTER 2 TYPES OF
TOXIC RESPONSES 15 2.1 ADAPTATION TO CELLULAR STRESS 16 2.2 TOXIC
RESPONSES 18 2.3 DISRUPTION OF CYTOPROTECTIVE MECHANISMS 19 LEARNING
POINTS 21 FURTHER READING 22 CHAPTER 3 ORGAN-SELECTIVE TOXICITY 23 3.1
BIOLOGICAL BASIS OF ORGAN-SELECTIVE TOXICITY 23 3.1.1 MOLECULAR HOMOLOGY
23 3.1.2 TISSUE-SELECTIVE TRANSCRIPTION FACTORS 25 3.1.3
TISSUE-RESTRICTED EXPRESSION OF MOLECULAR TARGETS 27 3.2 SELECTIVE
HEPATOTOXICITY AND NEPHROTOXICITY 31 3.2.1 XENOBIOTIC-BIOACTIVING
ENZYMES 32 3.2.2 VECTORIAL TRANSPORT OF XENOBIOTICS 33 LEARNING POINTS
36 FURTHER READING 37 CHAPTER 4 CELLULAR TRANSPORT AND SELECTIVE
ACCUMULATION OF POTENTIALLY TOXIC XENOBIOTICS 39 4.1 TRANSMEMBRANE
TRANSPORT OF XENOBIOTICS 39 4.2 CELL-SPECIFIC DELIVERY OF XENOBIOTICS TO
INTRACELLULAR TARGETS BY PHYSIOLOGICAL UPTAKE SYSTEMS 41 4.2.1
MULTISPECIFIC HEPATIC BILE SALT UPTAKE SYSTEMS 41 4.2.2 PULMONARY
EPITHELIAL-CELL POLYAMINE CARRIER 42 4.2.3 THE NEURONAL DOPAMINE
TRANSPORTER AND XENOBIOTIC-INDUCED PARKINSONISM 45 4.3 XENOBIOTIC EXPORT
PUMPS 48 4.3.1 HEPATOBILIARY CONJUGATE EXPORT PUMP AND CHOLESTASIS 49
4.3.2 MULTIDRUG RESISTANCE IN CANCER CELLS 52 4.3.3 PERMEABILITY OF THE
BLOOD-BRAIN BARRIER AND BLOOD-TESTIS BARRIER 54 LEARNING POINTS 58
FURTHER READING 58 CHAPTER 5 BIOACTIVATION OF XENOBIOTICS TO REACTIVE
METABOLITES 63 5.1 BIOTRANSFORMATION AND BIOACTIVATION/BIOINACTIVATION
63 5.2 PHASE I (FUNCTIONALIZATION) AND PHASE II (CONJUGATION) REACTIONS
64 5.2.1 CYTOCHROME P450 (CYP) 65 5.2.1.1 MECHANISMS AND TOXICOLOGICAL
CONSEQUENCES OF ISOFORM-SELECTIVE CYP INDUCTION 71 5.2.1.2 MECHANISMS
AND CONSEQUENCES OF ISOFORM-SELECTIVE CYP INHIBITION 74 5.2.1.3
BIOACTIVATION OF XENOBIOTICS BY CYP 76 5.2.2 PEROXIDASES 78 5.2.3
UDP-GLUCURONOSYLTRANSFERASE (UGT) 79 5.2.3.1 MECHANISMS AND
TOXICOLOGICAL CONSEQUENCES OF UGT INDUCTION 82 5.2.3.2 REACTIVE ACYL
GLUCURONIDES AND THEIR POSITIONAL ISOMERS 82 5.2.3.3 (V-GLUCURONIDATION
OF AROMATIC AMINES 83 5.2.4 SULFOTRANSFERASE (SULT) 86 5.2.5
/V-ACETYLTRANSFERASE (NAT) 88 5.2.5.1 BIOACTIVATION OF ARYLAMINES 89
5.2.5.2 TOXICOLOGICAL CONSEQUENCES OF INDIVIDUAL NAT EXPRESSION 90 5.2.6
GLUTATHIONE-S-TRANSFERASE (GST) 93 5.2.6.1 GLUTATHIONE CONJUGATION AS A
PROTECTIVE MECHANISM 93 5.2.6.2 BIOACTIVATION OF XENOBIOTICS BY GST 95
5.3 NET BALANCE OF BIOACTIVATION/BIOINACTIVATION FOR RISK ASSESSMENT 101
5.4 MECHANISMS OF PHOTOTOXICITY 104 5.5 PROTECTIVE MECHANISMS AGAINST
REACTIVE METABOLITES: THE STRESS RESPONSE 107 5.5.1 INDUCTION OF
HEAT-SHOCK PROTEINS 108 5.5.2 TARGETING OF STRESS-RESPONSE PROTEINS BY
REACTIVE METABOLITES 109 LEARNING POINTS 110 FURTHER READING 1 11
CHAPTER 6 XENOBIOTIC-INDUCED OXIDATIVE STRESS: CELL INJURY, SIGNALING,
AND GENE REGULATION 117 6.1 REACTIVE OXYGEN SPECIES (ROS) AND
OXIDOREDUCTIVE STRESS 117 6.1.1 MECHANISMS OF XENOBIOTIC-INDUCED
INTRACELLULAR ROS PRODUCTION 119 6.1.2 THE KEY PLAYERS: SUPEROXIDE ANION
RADICAL, HYDROGEN PEROXIDE, AND HYDROXYL RADICAL 125 6.1.3 ROLE OF IRON
AND OTHER REDOX-ACTIVE TRANSITION METALS 128 6.1.4 MECHANISMS OF
XENOBIOTIC-ENHANCED EXTRACELLULAR ROS PRODUCTION 132 6.1.5 OTHER ROS:
OZONE AND SINGLET OXYGEN 134 6.1.6 REACTIVE NITROGEN SPECIES (RNS) AND
OXIDATIVE STRESS 136 6.2 TOXICOLOGICAL CONSEQUENCES OF OXIDATIVE STRESS
138 6.2.1 OXIDATIVE DNA DAMAGE 139 6.2.2 OXIDATIVE PROTEIN DAMAGE......
142 6.2.3 OXIDATIVE LIPID DAMAGE 145 6.3 INTERFERENCE WITH ANTIOXIDANT
DEFENSE MECHANISMS 149 6.3.1 GLUTATHIONE 150 6.3.1.1 GSH-COUPLED ENZYME
SYSTEMS 151 6.3.1.2 GENETIC DEFICIENCY IN ERYTHROCYTE
GLUCOSE-6-PHOSPHATE DEHYDROGENASE 153 6.3.2 SUPEROXIDE DISMUTASE 157
6.3.3 METALLOTHIONEIN 158 6.3.4 A-TOCOPHEROL 161 6.4 INTRACELLULAR
SIGNALING AND GENE REGULATION BY OXIDATIVE STRESS 161 LEARNING POINTS
169 FURTHER READING 169 CHAPTER 7 DISRUPTION OF CELLULAR CALCIUM
HOMEOSTASIS 177 7.1 XENOBIOTIC-INDUCED ALTERATIONS IN INTRACELLULAR CA
2+ DISTRIBUTION 177 7.2 TOXICOLOGICAL CONSEQUENCES OF INCREASED
CYTOSOLIC CA :+ CONCENTRATIONS 179 LEARNING POINTS 183 FURTHER READING
184 CHAPTER 8 MECHANISMS OF NECROTIC AND APOPTOTIC CELL DEATH 185 8.1
NECROSIS 185 8.1.1 MECHANISMS OF NECROSIS 185 8.1.2 INITIATION AND
PROGRESSION OF NECROTIC TISSUE INJURY 186 8.2 APOPTOSIS 187 8.2.1
MOLECULAR MECHANISMS AND PATHWAYS OF APOPTOSIS 187 8.2.1.1 MOLECULAR
MECHANISMS OF APOPTOTIC CELL DEATH (I| 188 8.2.1.2 MOLECULAR MECHANISMS
OF APOPTOTIC CELL DEATH (II) 191 8.2.2 SIGNALING THROUGH DEATH RECEPTORS
192 8.2.3 CASPASES * THE EXECUTORS 196 8.2.4 ROLE OF MITOCHONDRIA 198
8.2.5 CHECKPOINTS * THE BCL-2 PROTEINS 201 8.2.6 SUPPRESSION OF
APOPTOSIS * TOXICOLOGICAL CONSEQUENCES 203 LEARNING POINTS 204 FURTHER
READING 205 CHAPTER 9 IMPAIRMENT OF CELL PROLIFERATION AND TISSUE REPAIR
209 9.1 THE CELL CYCLE 209 9.2 STIMULATION OF DNA SYNTHESIS AND CELL
PROLIFERATION: XENOBIOTICS AS MITOGENS 210 9.3 INHIBITION OF CELL
PROLIFERATION BY XENOBIOTICS 213 9.4 INHIBITION OF TISSUE REPAIR 215
LEARNING POINTS 218 FURTHER READING 219 CHAPTER 10 COVALENT BINDING OF
REACTIVE METABOLITES TO CELLULAR MACROMOLECULES 221 10.1 ELECTROPHILES
AND NUCLEOPHILIC TARGETS 221 10.2 COVALENT PROTEIN BINDING 223 10.2.1
SELECTIVITY OF COVALENT ADDUCT FORMATION 224 10.2.2 DOWNSTREAM
TOXICOLOGICAL CONSEQUENCES OF COVALENT PROTEIN BINDING 228 10.2.2.1
COVALENT MODIFICATION AND INACTIVATION OF PROTEIN PHOSPHATASES 229
10.2.2.2 COVALENT MODIFICATION OF NEUROFILAMENTS 233 10.2.2.3 COVALENT
MODIFICATION OF PROTEINS IN THE BILIARY TREE AND SMALL INTESTINE 238
10.3 COVALENT DNA BINDING 242 10.3.1 TOXICOLOGICAL CONSEQUENCES OF DNA
ALKYLATION 243 LEARNING POINTS 245 FURTHER READING 246 CHAPTER 11 IMMUNE
MECHANISMS 251 11.1 XENOBIOTIC-INDUCED ACTIVATION OF THE INNATE IMMUNE
SYSTEM 252 11.2 IMMUNOSUPPRESSION BY XENOBIOTICS 256 11.3
IMMUNE-MEDIATED TOXICITY 260 11.3.1 AUTOIMMUNE REACTIONS 265 11.3.2
IMMUNOALLERGY 267 11.3.3 IDIOSYNCRATIC REACTIONS AND THE DANGER
HYPOTHESIS 274 LEARNING POINTS 276 FURTHER READING 277 CHAPTER 12
CYTOKINE-MEDIATED TOXICITY 281 12.1 TUMOR NECROSIS FACTOR-A AND OTHER
PROINFLAMMATORY CYTOKINES 282 12.2 CHEMOKINES AND INFLAMMATORY CELL
RECRUITMENT 285 LEARNING POINTS 287 FURTHER READING 288 CHAPTER 13
SPECIFIC INACTIVATION OF ENZYMES AND OTHER PROTEINS 289 13.1
INACTIVATION OF THIOL-CONTAINING ENZYMES 289 13.2 DISRUPTION OF
ACETYLCHOLINESTERASE ACTIVITY 289 13.3 TRANSTHYRETIN BINDING AND
INACTIVATION: DISRUPTION OF THYROID FUNCTION 294 13.4 INACTIVATION OF
DNA-MISMATCH-REPAIR PROTEINS 296 LEARNING POINTS 298 FURTHER READING 299
CHAPTER 14 INTERACTIONS OF XENOBIOTICS WITH ION TRANSPORTERS 301 14.1
INTERACTIONS WITH NEURONAL NA + CHANNELS 301 14.2 INTERACTIONS WITH THE
NA + /K + PUMP 303 14.3 SELECTIVE INHIBITION OF CARDIAC MYOCYTE K +
CHANNELS AND QT PROLONGATION 305 LEARNING POINTS 307 FURTHER READING 308
CHAPTER 15 NUCLEAR RECEPTOR-MEDIATED TOXICITY 309 15.1 THE ARYL
HYDROCARBON RECEPTOR (AHR) 310 15.1.1 AHR-MEDIATED TOXICITY OF
POLYCHLORINATED DIBENZODIOXINS, DIBENZOFURANS, AND BIPHENYLS 311 15.2
XENOESTROGENS AND ANTIANDROGENS 317 15.2.1 ESTROGEN-RECEPTOR
(ER)-MEDIATED TOXICITY 318 15.2.2 ANDROGEN RECEPTOR (AR)-MEDIATED
TOXICITY 321 15.3 PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPARS)
324 15.3.1 PPARA-DEPENDENT TOXICITY 326 15.3.2 PPARY-MEDIATED TOXICITY
328 15.4 RETINOIC ACID RECEPTOR (RAR) 332 LEARNING POINTS 334 FURTHER
READING 335 CHAPTER 16 ACTIVATION OR DISRUPTION OF CELLULAR SIGNAL
TRANSDUCTION BY XENOBIOTICS 341 16.1 SIGNALING: SENSING AND RESPONDING
341 16.1.1 THE RECEPTORS 342 16.1.2 THE SIGNALING PATHWAYS 343 16.2
INTERFERENCE WITH SIGNAL TRANSDUCTION BY XENOBIOTICS 345 16.2.1
DISRUPTION OF G-PROTEIN-COUPLED RECEPTOR FUNCTION 346 16.2.2 PROTEIN
KINASE SIGNALING PATHWAYS 347 16.2.2.1 MULTIPLE ACTIVATION OF PROTEIN
KINASE SIGNALING PATHWAYS 347 16.2.2.2 ACTIVATION OF PROTEIN KINASE
SIGNAL TRANSDUCTION PATHWAYS BY FOREIGN SIGNALING PATHWAYS 347
16.2.2.3 ACTIVATION OF PROTEIN KINASE PATHWAYS BY INACTIVATION OF
PHOSPHATASES 348 16.2.2.4 INACTIVATION OF SELECTIVE MAPK SIGNAL
TRANSDUCTION PATHWAYS 349 16.2.2.5 ACTIVATION AND INACTIVATION OF JNK
AND ITS ROLE IN MITOCHONDRIA-MEDIATED CELL DEATH 350 16.2.3 DISRUPTION
OF SENSOR (TRANSCRIPTION FACTOR) FUNCTION 353 LEARNING POINTS 355
FURTHER READING 355 CHAPTER 17 DISRUPTION OF MITOCHONDRIAL FUNCTION AND
MITOCHONDRIA- MEDIATED TOXICITY 357 17.1 MITOCHONDRIAL TARGETS AND
XENOBIOTIC-INDUCED BIOENERGY CRISIS 357 17.2 PROTONOPHORETIC AND
UNCOUPLING ACTIVITY OF XENOBIOTICS 360 17.3 INHIBITION OF NADH
PRODUCTION 362 17.3.1 INHIBITION OF MITOCHONDRIAL FATTY ACYL
(3-OXIDATION 362 17.3.2 XENOBIOTICS AS PSEUDOSUBSTRATES FOR THE CITRATE
CYCLE 365 17.4 INHIBITION OF THE ELECTRON TRANSPORT CHAIN AND INCREASED
GENERATION OF ROS 366 17.5 MITOCHONDRIAL MEMBRANE PERMEABILIZATION 372
17.5.1 INDUCTION OF THE MITOCHONDRIAL OUTER-MEMBRANE PERMEABILIZATION
(MOMP) 372 17.5.2 OPENING OF THE MITOCHONDRIAL MEMBRANE PERMEABILITY
TRANSITION (MPT) PORE 372 17.6 SELECTIVE DEPLETION OF MITOCHONDRIAL DNA
377 LEARNING POINTS 380 FURTHER READING 381 CHAPTER 18 NOVEL MECHANISMS
DERIVED FROM SYSTEMS TOXICOLOGY 385 LEARNING POINTS 389 FURTHER READING
389 INDEX 391
|
| adam_txt |
SECOND EDITION MECHANISTIC TOXICOLOGY THE MOLECULAR BASIS OF HOW
CHEMICALS DISRUPT BIOLOGICAL TARGETS URS A. BOELSTERLI CRC PRESS TAVLOR
& FRANCE CROUP CRC PRESS IS AN IMP^T O* :H TAYLOR H FRANCN C'R,,JP I A"
. CONTENTS CHAPTER 1 INTRODUCTION 1 1.1 WHY MOLECULAR MECHANISMS? 1 1.2
TOXICOKINETICS AND TOXICODYNAMICS 5 1.2.1 TOXICOKINETIC FACTORS AS BASIC
MECHANISMS OF TOXICITY 6 1.2.2 TOXICODYNAMIC FACTORS AS BASIC MECHANISMS
OF TOXICITY 7 LEARNING POINTS 12 FURTHER READING 13 CHAPTER 2 TYPES OF
TOXIC RESPONSES 15 2.1 ADAPTATION TO CELLULAR STRESS 16 2.2 TOXIC
RESPONSES 18 2.3 DISRUPTION OF CYTOPROTECTIVE MECHANISMS 19 LEARNING
POINTS 21 FURTHER READING 22 CHAPTER 3 ORGAN-SELECTIVE TOXICITY 23 3.1
BIOLOGICAL BASIS OF ORGAN-SELECTIVE TOXICITY 23 3.1.1 MOLECULAR HOMOLOGY
23 3.1.2 TISSUE-SELECTIVE TRANSCRIPTION FACTORS 25 3.1.3
TISSUE-RESTRICTED EXPRESSION OF MOLECULAR TARGETS 27 3.2 SELECTIVE
HEPATOTOXICITY AND NEPHROTOXICITY 31 3.2.1 XENOBIOTIC-BIOACTIVING
ENZYMES 32 3.2.2 VECTORIAL TRANSPORT OF XENOBIOTICS 33 LEARNING POINTS
36 FURTHER READING 37 CHAPTER 4 CELLULAR TRANSPORT AND SELECTIVE
ACCUMULATION OF POTENTIALLY TOXIC XENOBIOTICS 39 4.1 TRANSMEMBRANE
TRANSPORT OF XENOBIOTICS 39 4.2 CELL-SPECIFIC DELIVERY OF XENOBIOTICS TO
INTRACELLULAR TARGETS BY PHYSIOLOGICAL UPTAKE SYSTEMS 41 4.2.1
MULTISPECIFIC HEPATIC BILE SALT UPTAKE SYSTEMS 41 4.2.2 PULMONARY
EPITHELIAL-CELL POLYAMINE CARRIER 42 4.2.3 THE NEURONAL DOPAMINE
TRANSPORTER AND XENOBIOTIC-INDUCED PARKINSONISM 45 4.3 XENOBIOTIC EXPORT
PUMPS 48 4.3.1 HEPATOBILIARY CONJUGATE EXPORT PUMP AND CHOLESTASIS 49
4.3.2 MULTIDRUG RESISTANCE IN CANCER CELLS 52 4.3.3 PERMEABILITY OF THE
BLOOD-BRAIN BARRIER AND BLOOD-TESTIS BARRIER 54 LEARNING POINTS 58
FURTHER READING 58 CHAPTER 5 BIOACTIVATION OF XENOBIOTICS TO REACTIVE
METABOLITES 63 5.1 BIOTRANSFORMATION AND BIOACTIVATION/BIOINACTIVATION
63 5.2 PHASE I (FUNCTIONALIZATION) AND PHASE II (CONJUGATION) REACTIONS
64 5.2.1 CYTOCHROME P450 (CYP) 65 5.2.1.1 MECHANISMS AND TOXICOLOGICAL
CONSEQUENCES OF ISOFORM-SELECTIVE CYP INDUCTION 71 5.2.1.2 MECHANISMS
AND CONSEQUENCES OF ISOFORM-SELECTIVE CYP INHIBITION 74 5.2.1.3
BIOACTIVATION OF XENOBIOTICS BY CYP 76 5.2.2 PEROXIDASES 78 5.2.3
UDP-GLUCURONOSYLTRANSFERASE (UGT) 79 5.2.3.1 MECHANISMS AND
TOXICOLOGICAL CONSEQUENCES OF UGT INDUCTION 82 5.2.3.2 REACTIVE ACYL
GLUCURONIDES AND THEIR POSITIONAL ISOMERS 82 5.2.3.3 (V-GLUCURONIDATION
OF AROMATIC AMINES 83 5.2.4 SULFOTRANSFERASE (SULT) 86 5.2.5
/V-ACETYLTRANSFERASE (NAT) 88 5.2.5.1 BIOACTIVATION OF ARYLAMINES 89
5.2.5.2 TOXICOLOGICAL CONSEQUENCES OF INDIVIDUAL NAT EXPRESSION 90 5.2.6
GLUTATHIONE-S-TRANSFERASE (GST) 93 5.2.6.1 GLUTATHIONE CONJUGATION AS A
PROTECTIVE MECHANISM 93 5.2.6.2 BIOACTIVATION OF XENOBIOTICS BY GST 95
5.3 NET BALANCE OF BIOACTIVATION/BIOINACTIVATION FOR RISK ASSESSMENT 101
5.4 MECHANISMS OF PHOTOTOXICITY 104 5.5 PROTECTIVE MECHANISMS AGAINST
REACTIVE METABOLITES: THE STRESS RESPONSE 107 5.5.1 INDUCTION OF
HEAT-SHOCK PROTEINS 108 5.5.2 TARGETING OF STRESS-RESPONSE PROTEINS BY
REACTIVE METABOLITES 109 LEARNING POINTS 110 FURTHER READING 1 11
CHAPTER 6 XENOBIOTIC-INDUCED OXIDATIVE STRESS: CELL INJURY, SIGNALING,
AND GENE REGULATION 117 6.1 REACTIVE OXYGEN SPECIES (ROS) AND
OXIDOREDUCTIVE STRESS 117 6.1.1 MECHANISMS OF XENOBIOTIC-INDUCED
INTRACELLULAR ROS PRODUCTION 119 6.1.2 THE KEY PLAYERS: SUPEROXIDE ANION
RADICAL, HYDROGEN PEROXIDE, AND HYDROXYL RADICAL 125 6.1.3 ROLE OF IRON
AND OTHER REDOX-ACTIVE TRANSITION METALS 128 6.1.4 MECHANISMS OF
XENOBIOTIC-ENHANCED EXTRACELLULAR ROS PRODUCTION 132 6.1.5 OTHER ROS:
OZONE AND SINGLET OXYGEN 134 6.1.6 REACTIVE NITROGEN SPECIES (RNS) AND
OXIDATIVE STRESS 136 6.2 TOXICOLOGICAL CONSEQUENCES OF OXIDATIVE STRESS
138 6.2.1 OXIDATIVE DNA DAMAGE 139 6.2.2 OXIDATIVE PROTEIN DAMAGE.
142 6.2.3 OXIDATIVE LIPID DAMAGE 145 6.3 INTERFERENCE WITH ANTIOXIDANT
DEFENSE MECHANISMS 149 6.3.1 GLUTATHIONE 150 6.3.1.1 GSH-COUPLED ENZYME
SYSTEMS 151 6.3.1.2 GENETIC DEFICIENCY IN ERYTHROCYTE
GLUCOSE-6-PHOSPHATE DEHYDROGENASE 153 6.3.2 SUPEROXIDE DISMUTASE 157
6.3.3 METALLOTHIONEIN 158 6.3.4 A-TOCOPHEROL 161 6.4 INTRACELLULAR
SIGNALING AND GENE REGULATION BY OXIDATIVE STRESS 161 LEARNING POINTS
169 FURTHER READING 169 CHAPTER 7 DISRUPTION OF CELLULAR CALCIUM
HOMEOSTASIS 177 7.1 XENOBIOTIC-INDUCED ALTERATIONS IN INTRACELLULAR CA
2+ DISTRIBUTION 177 7.2 TOXICOLOGICAL CONSEQUENCES OF INCREASED
CYTOSOLIC CA :+ CONCENTRATIONS 179 LEARNING POINTS 183 FURTHER READING
184 CHAPTER 8 MECHANISMS OF NECROTIC AND APOPTOTIC CELL DEATH 185 8.1
NECROSIS 185 8.1.1 MECHANISMS OF NECROSIS 185 8.1.2 INITIATION AND
PROGRESSION OF NECROTIC TISSUE INJURY 186 8.2 APOPTOSIS 187 8.2.1
MOLECULAR MECHANISMS AND PATHWAYS OF APOPTOSIS 187 8.2.1.1 MOLECULAR
MECHANISMS OF APOPTOTIC CELL DEATH (I| 188 8.2.1.2 MOLECULAR MECHANISMS
OF APOPTOTIC CELL DEATH (II) 191 8.2.2 SIGNALING THROUGH DEATH RECEPTORS
192 8.2.3 CASPASES * THE EXECUTORS 196 8.2.4 ROLE OF MITOCHONDRIA 198
8.2.5 CHECKPOINTS * THE BCL-2 PROTEINS 201 8.2.6 SUPPRESSION OF
APOPTOSIS * TOXICOLOGICAL CONSEQUENCES 203 LEARNING POINTS 204 FURTHER
READING 205 CHAPTER 9 IMPAIRMENT OF CELL PROLIFERATION AND TISSUE REPAIR
209 9.1 THE CELL CYCLE 209 9.2 STIMULATION OF DNA SYNTHESIS AND CELL
PROLIFERATION: XENOBIOTICS AS MITOGENS 210 9.3 INHIBITION OF CELL
PROLIFERATION BY XENOBIOTICS 213 9.4 INHIBITION OF TISSUE REPAIR 215
LEARNING POINTS 218 FURTHER READING 219 CHAPTER 10 COVALENT BINDING OF
REACTIVE METABOLITES TO CELLULAR MACROMOLECULES 221 10.1 ELECTROPHILES
AND NUCLEOPHILIC TARGETS 221 10.2 COVALENT PROTEIN BINDING 223 10.2.1
SELECTIVITY OF COVALENT ADDUCT FORMATION 224 10.2.2 DOWNSTREAM
TOXICOLOGICAL CONSEQUENCES OF COVALENT PROTEIN BINDING 228 10.2.2.1
COVALENT MODIFICATION AND INACTIVATION OF PROTEIN PHOSPHATASES 229
10.2.2.2 COVALENT MODIFICATION OF NEUROFILAMENTS 233 10.2.2.3 COVALENT
MODIFICATION OF PROTEINS IN THE BILIARY TREE AND SMALL INTESTINE 238
10.3 COVALENT DNA BINDING 242 10.3.1 TOXICOLOGICAL CONSEQUENCES OF DNA
ALKYLATION 243 LEARNING POINTS 245 FURTHER READING 246 CHAPTER 11 IMMUNE
MECHANISMS 251 11.1 XENOBIOTIC-INDUCED ACTIVATION OF THE INNATE IMMUNE
SYSTEM 252 11.2 IMMUNOSUPPRESSION BY XENOBIOTICS 256 11.3
IMMUNE-MEDIATED TOXICITY 260 11.3.1 AUTOIMMUNE REACTIONS 265 11.3.2
IMMUNOALLERGY 267 11.3.3 IDIOSYNCRATIC REACTIONS AND THE "DANGER"
HYPOTHESIS 274 LEARNING POINTS 276 FURTHER READING 277 CHAPTER 12
CYTOKINE-MEDIATED TOXICITY 281 12.1 TUMOR NECROSIS FACTOR-A AND OTHER
PROINFLAMMATORY CYTOKINES 282 12.2 CHEMOKINES AND INFLAMMATORY CELL
RECRUITMENT 285 LEARNING POINTS 287 FURTHER READING 288 CHAPTER 13
SPECIFIC INACTIVATION OF ENZYMES AND OTHER PROTEINS 289 13.1
INACTIVATION OF THIOL-CONTAINING ENZYMES 289 13.2 DISRUPTION OF
ACETYLCHOLINESTERASE ACTIVITY 289 13.3 TRANSTHYRETIN BINDING AND
INACTIVATION: DISRUPTION OF THYROID FUNCTION 294 13.4 INACTIVATION OF
DNA-MISMATCH-REPAIR PROTEINS 296 LEARNING POINTS 298 FURTHER READING 299
CHAPTER 14 INTERACTIONS OF XENOBIOTICS WITH ION TRANSPORTERS 301 14.1
INTERACTIONS WITH NEURONAL NA + CHANNELS 301 14.2 INTERACTIONS WITH THE
NA + /K + PUMP 303 14.3 SELECTIVE INHIBITION OF CARDIAC MYOCYTE K +
CHANNELS AND QT PROLONGATION 305 LEARNING POINTS 307 FURTHER READING 308
CHAPTER 15 NUCLEAR RECEPTOR-MEDIATED TOXICITY 309 15.1 THE ARYL
HYDROCARBON RECEPTOR (AHR) 310 15.1.1 AHR-MEDIATED TOXICITY OF
POLYCHLORINATED DIBENZODIOXINS, DIBENZOFURANS, AND BIPHENYLS 311 15.2
XENOESTROGENS AND ANTIANDROGENS 317 15.2.1 ESTROGEN-RECEPTOR
(ER)-MEDIATED TOXICITY 318 15.2.2 ANDROGEN RECEPTOR (AR)-MEDIATED
TOXICITY 321 15.3 PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPARS)
324 15.3.1 PPARA-DEPENDENT TOXICITY 326 15.3.2 PPARY-MEDIATED TOXICITY
328 15.4 RETINOIC ACID RECEPTOR (RAR) 332 LEARNING POINTS 334 FURTHER
READING 335 CHAPTER 16 ACTIVATION OR DISRUPTION OF CELLULAR SIGNAL
TRANSDUCTION BY XENOBIOTICS 341 16.1 SIGNALING: SENSING AND RESPONDING
341 16.1.1 THE RECEPTORS 342 16.1.2 THE SIGNALING PATHWAYS 343 16.2
INTERFERENCE WITH SIGNAL TRANSDUCTION BY XENOBIOTICS 345 16.2.1
DISRUPTION OF G-PROTEIN-COUPLED RECEPTOR FUNCTION 346 16.2.2 PROTEIN
KINASE SIGNALING PATHWAYS 347 16.2.2.1 MULTIPLE ACTIVATION OF PROTEIN
KINASE SIGNALING PATHWAYS 347 16.2.2.2 ACTIVATION OF PROTEIN KINASE
SIGNAL TRANSDUCTION PATHWAYS BY "FOREIGN" SIGNALING PATHWAYS 347
16.2.2.3 ACTIVATION OF PROTEIN KINASE PATHWAYS BY INACTIVATION OF
PHOSPHATASES 348 16.2.2.4 INACTIVATION OF SELECTIVE MAPK SIGNAL
TRANSDUCTION PATHWAYS 349 16.2.2.5 ACTIVATION AND INACTIVATION OF JNK
AND ITS ROLE IN MITOCHONDRIA-MEDIATED CELL DEATH 350 16.2.3 DISRUPTION
OF SENSOR (TRANSCRIPTION FACTOR) FUNCTION 353 LEARNING POINTS 355
FURTHER READING 355 CHAPTER 17 DISRUPTION OF MITOCHONDRIAL FUNCTION AND
MITOCHONDRIA- MEDIATED TOXICITY 357 17.1 MITOCHONDRIAL TARGETS AND
XENOBIOTIC-INDUCED BIOENERGY CRISIS 357 17.2 PROTONOPHORETIC AND
UNCOUPLING ACTIVITY OF XENOBIOTICS 360 17.3 INHIBITION OF NADH
PRODUCTION 362 17.3.1 INHIBITION OF MITOCHONDRIAL FATTY ACYL
(3-OXIDATION 362 17.3.2 XENOBIOTICS AS PSEUDOSUBSTRATES FOR THE CITRATE
CYCLE 365 17.4 INHIBITION OF THE ELECTRON TRANSPORT CHAIN AND INCREASED
GENERATION OF ROS 366 17.5 MITOCHONDRIAL MEMBRANE PERMEABILIZATION 372
17.5.1 INDUCTION OF THE MITOCHONDRIAL OUTER-MEMBRANE PERMEABILIZATION
(MOMP) 372 17.5.2 OPENING OF THE MITOCHONDRIAL MEMBRANE PERMEABILITY
TRANSITION (MPT) PORE 372 17.6 SELECTIVE DEPLETION OF MITOCHONDRIAL DNA
377 LEARNING POINTS 380 FURTHER READING 381 CHAPTER 18 NOVEL MECHANISMS
DERIVED FROM SYSTEMS TOXICOLOGY 385 LEARNING POINTS 389 FURTHER READING
389 INDEX 391 |
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| author | Boelsterli, Urs A. |
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| bvnumber | BV022870432 |
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| callnumber-raw | RA1220.3 |
| callnumber-search | RA1220.3 |
| callnumber-sort | RA 41220.3 |
| callnumber-subject | RA - Public Medicine |
| classification_rvk | VT 5300 |
| ctrlnum | (OCoLC)74459862 (DE-599)BVBBV022870432 |
| dewey-full | 615.9 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 615 - Pharmacology and therapeutics |
| dewey-raw | 615.9 |
| dewey-search | 615.9 |
| dewey-sort | 3615.9 |
| dewey-tens | 610 - Medicine and health |
| discipline | Chemie / Pharmazie Medizin |
| discipline_str_mv | Chemie / Pharmazie Medizin |
| edition | 2. ed. |
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| id | DE-604.BV022870432 |
| illustrated | Illustrated |
| index_date | 2024-07-02T18:47:02Z |
| indexdate | 2024-07-09T21:07:23Z |
| institution | BVB |
| isbn | 0849372720 9780849372728 |
| language | English |
| lccn | 2006035219 |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-016075542 |
| oclc_num | 74459862 |
| open_access_boolean | |
| owner | DE-19 DE-BY-UBM DE-20 |
| owner_facet | DE-19 DE-BY-UBM DE-20 |
| physical | 399 S. Ill., graph. Darst. cm |
| publishDate | 2009 |
| publishDateSearch | 2009 |
| publishDateSort | 2009 |
| publisher | CRC Press |
| record_format | marc |
| spelling | Boelsterli, Urs A. Verfasser aut Mechanistic toxicology the molecular basis of how chemicals disrupt biological targets Urs A. Boelsterli 2. ed. Boca Raton CRC Press 2009 399 S. Ill., graph. Darst. cm txt rdacontent n rdamedia nc rdacarrier Includes bibliographical references and index Biologia molecular larpcal Toxicologia larpcal Toxicologie moléculaire Transdução de sinal celular larpcal Molecular toxicology Toxicology methods Molecular Biology methods Signal Transduction Xenobiotics pharmacokinetics Xenobiotics toxicity http://www.loc.gov/catdir/enhancements/fy0703/2006035219-d.html Publisher description GBV Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016075542&sequence=000005&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Boelsterli, Urs A. Mechanistic toxicology the molecular basis of how chemicals disrupt biological targets Biologia molecular larpcal Toxicologia larpcal Toxicologie moléculaire Transdução de sinal celular larpcal Molecular toxicology Toxicology methods Molecular Biology methods Signal Transduction Xenobiotics pharmacokinetics Xenobiotics toxicity |
| title | Mechanistic toxicology the molecular basis of how chemicals disrupt biological targets |
| title_auth | Mechanistic toxicology the molecular basis of how chemicals disrupt biological targets |
| title_exact_search | Mechanistic toxicology the molecular basis of how chemicals disrupt biological targets |
| title_exact_search_txtP | Mechanistic toxicology the molecular basis of how chemicals disrupt biological targets |
| title_full | Mechanistic toxicology the molecular basis of how chemicals disrupt biological targets Urs A. Boelsterli |
| title_fullStr | Mechanistic toxicology the molecular basis of how chemicals disrupt biological targets Urs A. Boelsterli |
| title_full_unstemmed | Mechanistic toxicology the molecular basis of how chemicals disrupt biological targets Urs A. Boelsterli |
| title_short | Mechanistic toxicology |
| title_sort | mechanistic toxicology the molecular basis of how chemicals disrupt biological targets |
| title_sub | the molecular basis of how chemicals disrupt biological targets |
| topic | Biologia molecular larpcal Toxicologia larpcal Toxicologie moléculaire Transdução de sinal celular larpcal Molecular toxicology Toxicology methods Molecular Biology methods Signal Transduction Xenobiotics pharmacokinetics Xenobiotics toxicity |
| topic_facet | Biologia molecular Toxicologia Toxicologie moléculaire Transdução de sinal celular Molecular toxicology Toxicology methods Molecular Biology methods Signal Transduction Xenobiotics pharmacokinetics Xenobiotics toxicity |
| url | http://www.loc.gov/catdir/enhancements/fy0703/2006035219-d.html http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016075542&sequence=000005&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT boelsterliursa mechanistictoxicologythemolecularbasisofhowchemicalsdisruptbiologicaltargets |