Biological Reactive Intermediates IV: Molecular and Cellular Effects and Their Impact on Human Health

Front Matter....Pages i-xvii
Cytochrome P-450 Oxidations and the Generation of Biologically Reactive Intermediates....Pages 1-11
Formation of Reactive Intermediates by Phase II Enzymes: Glutathione-Dependent Bioactivation Reactions....Pages 13-24
Role of the Well-Known Basic and Recently Discovered Acidic Glutathione S-Transferases in the Control of Genotoxic Metabolites....Pages 25-39
Bioactivation of Xenobiotics by Flavin-Containing Monooxygenases....Pages 41-50
Formation of Biological Reactive Intermediates by Peroxidases: Halide Mediated Acetaminophen Oxidation and Cytotoxicity....Pages 51-64
Peroxyl Free Radicals: Biological Reactive Intermediates Produced during Lipid Oxidation....Pages 65-70
Biological Significance of Active Oxygen Species: In Vitro Studies on Singlet Oxygen-Induced DNA Damage and on the Singlet Oxygen Quenching Ability of Carotenoids, Tocopherols and Thiols....Pages 71-77
Physiological and Toxicological Roles of Hydroperoxides....Pages 79-86
Overview: Theoretical Aspects of Isotope Effects on the Pattern of Metabolites Formed by Cytochrome P-450....Pages 87-94
S-Thiolation of Protein Sulfhydryls....Pages 95-103
Cytochrome P-450 as a Target of Biological Reactive Intermediates....Pages 105-109
Hapten Carrier Conjugates Associated with Halothane Hepatitis....Pages 111-120
Metabolism of Drugs by Activated Leukocytes: Implications for Drug-Induced Lupus and Other Drug Hypersensitivity Reactions....Pages 121-132
Formation of Reactive Metabolites and Appearance of Antiorganelle Antibodies in Man....Pages 133-137
Formation of a Protein-Acetaldehyde Adduct in Liver during Chronic Alcohol Exposure....Pages 139-149
Dose-Response Relationships in Chemical Carcinogenesis: From DNA Adducts to Tumor Incidence....Pages 151-156
The Single Cell Gel (SCG) Assay: An Electrophoretic Technique for the Detection of DNA Damage in Individual Cells....Pages 157-164
Monitoring Human Exposure to Environmental Carcinogens....Pages 165-181
Comparing the Frequency and Spectra of Mutations Induced When an SV40-Based Shuttle Vector Containing Covalently Bound Residues of Structurally-Related Carcinogens Replicates in Human Cells....Pages 183-191
Molecular Targets of Chemical Mutagens....Pages 193-209
Mutagenic Consequences of the Alteration of DNA by Chemicals and Radiation....Pages 211-223
Gene Specific Damage and Repair after Treatment of Cells with UV and Chemotherapeutical Agents....Pages 225-233
Proto-Oncogene Activation in Rodent and Human Tumors....Pages 235-243
Toxicity of 3-Methyleneoxindole, a Proposed Reactive Intermediate in the Metabolism of 3-Methylindole....Pages 245-248
The Role of Cytochrome P450IIE1 in Bioactivation of Acetaminophen in Diabetic and Acetone-Treated Mice....Pages 249-251
Arylamine-Induced Hemolytic Anemia: Electron Spin Resonance Spectrometry Studies....Pages 253-255
Selective Alterations in the Profiles of Newly Synthesized Proteins by Acetaminophen (APAP) and its Dimethylated Analogues: Relationship to Oxidative Stress....Pages 257-260
Benzene Metabolism by Two Purified, Reconstituted Rat Hepatic Mixed Function Oxidase Systems....Pages 261-265
Stereochemical Induction of Cytochrome P450IVA1 (P452) and Peroxisome Proliferation in Male Rat....Pages 267-270
Cyanide Liberation and Oxidative Stress by Organothiocyanates, Organonitriles and Nitroprusside in Isolated Hepatocytes....Pages 271-274
Mixed Function Oxidase Enzyme Responses to in Vivo and in Vitro Chromate Treatment....Pages 275-280
Fatty Acid β-Oxidation-Dependent Bioactivation of 5,6-Dichloro-4-Thia-5-Hexenoate and Analogs in Isolated Rat Hepatocytes....Pages 281-284
Role of the Acetone Inducible P-450IIE1 in the Deethylation of Diethylnitrosamine in Hamster....Pages 285-287
Stereochemistry of the Microsomal Glutathione S -Transferase-Catalyzed Addition of Glutathione to Chlorotrifluoroethene in Isolated Rat Hepatocytes....Pages 289-293
The Pathophysiological Significance of Reactive Oxygen Formation in Rat Liver....Pages 295-298
Oxidative Stress during Hypoxia in Isolated-Perfused Rat Heart....Pages 299-304
Alteration of Growth Rate and Fibronectin by Imbalances in Superoxide Dismutase and Glutathione Peroxidase Activity....Pages 305-309
The Antidotal Activity of the Thiol Drug Diethyldithiocarbamate Against N-Acetyl-p-Benzoquinone Imine in Isolated Hepatocytes....Pages 311-314
Two Classes of Azo Dye Reductase Activity Associated with Rat Liver Microsomal Cytochrome P-450....Pages 315-321
Expression of a cDNA Encoding Rat Liver DT-Diaphorase in Escherichia Coli ....Pages 323-327
Suicidal Inactivation of Cytochrome P-450 by Halothane and Carbon Tetrachloride....Pages 329-332
Structure-Activity Relationships of Acrylate Esters: Reactivity Towards Glutathione and Hydrolysis by Carboxylesterase in Vitro ....Pages 333-335
Glutathione Conjugates of Hydralazine Formed in Theperoxidase/Hydrogen Peroxide/Glutathione System....Pages 337-342
Contribution of 3,4-Dichlorophenylhydroxylamine in Propanil-Induced Hemolytic Anemia....Pages 343-345
A Reduction in Mixed Function Oxidases and in Tumor Promoting Effects of Ethanol in a NDEA-Initiated Hepatocarcinogenesis Model....Pages 347-352
Selective Inducers of the Coh-Locus Enhance the Metabolisms of Coumarin- and of Quinoline-Derivatives but Not That of Naphthalenes....Pages 353-357
Primaquine-Induced Oxidative Stress in Isolated Hepatocytes as a Result of Reductive Activation....Pages 359-363
Nitroprusside: A Potpourri of Biologically Reactive Intermediates....Pages 365-369
Denitrosation of N -Nitrosodimethylamine in the Rat in Vivo ....Pages 371-375
Effect of Phenol and Catechol on the Kinetics of Human Myeloperoxidase-Dependent Hydroquinone Metabolism....Pages 377-381
Activation of 1-Hydroxymethylpyrene to an Electrophilic and Mutagenic Metabolite by Rat Hepatic Sulfotransferase Activity....Pages 383-391
Bioactivation of 2,6-Di-Tert-Butyl-4-Methyl Phenol (BHT) and Hydroxylated Analogues to Toxic Quinoid Metabolites....Pages 393-398
Further Evidence for the Role of Myeloperoxidase in the Activation of Benzo[A]Pyrene-7,8-Dihydrodiol by Polymorpho-Nuclear Leukocytesm....Pages 399-401
Quinones and their Glutathione Conjugates as Irreversible Inhibitors of Glutathione S-Transferases....Pages 403-406
Cytochrome P450 IA2 Activity in Man Measured by Caffeine Metabolism: Effect of Smoking, Broccoli and Exercise....Pages 407-411
Tissue Difference in Expression of Cytochrome P-450 between Liver and Lung of Syrian Golden Hamsters Treated with 3- Methylcholanthrene....Pages 413-417
Role of Calcium in Toxic and Programmed Cell Death....Pages 419-425
Molecular Mechanisms of y -Diketone Neuropathy....Pages 427-431
Microtubule Assembly is Altered Following Covalent Modification by the n -Hexane Metabolite 2,5-Hexanedione....Pages 433-442
The Role of Hepatic Metabolites of Benzene in Bone Marrow Peroxidase-Mediated Myelo- and Genotoxicity....Pages 443-455
Glutathione Conjugation as a Mechanism of Targeting Latent Quinones to the Kidney....Pages 457-464
Hepatic Bioactivation of 4-Vinylcyclohexene to Ovotoxic Epoxides....Pages 465-470
Testicular Metabolism and Toxicity of Halogenated Propanes....Pages 471-476
Lung Vascular Injury from Monocrotaline Pyrrole, a Putative Hepatic Metabolite....Pages 477-487
Reactive Oxygen Species in the Progression of CCl 4 -Induced Liver Injury....Pages 489-497
Parenchymal and Nonparenchymal Cell Interactions in Hepatotoxicity....Pages 499-505
Signal Paths and Regulation of Superoxide, Eicosanoid and Cytokine Formation in Macrophages of Rat Liver....Pages 507-520
Reactive Metabolites from N-Nitrosamines....Pages 521-524
Bisfuranoid Mycotoxins: Their Genotoxicity and Carcinogenicity....Pages 525-532
Covalent Bonding of Bay-Region Diol Epoxides to Nucleic Acids....Pages 533-553
Electrophilic Sulfuric Acid Ester Metabolites of Hydroxy-Methyl Aromatic Hydrocarbons as Precursors of Hepatic Benzylic DNA Adducts in Vivo....Pages 555-567
Heterocyclic Amines: New Mutagens and Carcinogenes in Cooked Foods....Pages 569-578
Acetaminophen and Protein Thiol Modification....Pages 579-588
Formation and Reactivity of a Quinone Methide in Biological Systems....Pages 589-596
Mechanisms for Pyrrolizidine Alkaloid Activation and Detoxification....Pages 597-603
Sulfur Conjugates as Putative Pneumotoxic Metabolites of the Pyrrolizidine Alkaloid, Monocrotaline....Pages 605-612
The Metabolism of Benzene to Muconic Acid, a Potential Biological Marker of Benzene Exposure....Pages 613-618
Lessons on the Second Cancers Resulting from Cancer Chemotherapy....Pages 619-625
Genetic Polymorphism of Drug Metabolism in Humans....Pages 627-640
Human Health Risk Assessment and Biological Reactive Intermediates: Hemoglobin Binding....Pages 641-647
Quantitating the Production of Biological Reactive Intermediates in Target Tissues: Example, Dichloromethane....Pages 649-655
Trapping of Reactive Intermediates by Incorporation of 14 C-Sodium Cyanide during Microsomal Oxidation....Pages 657-664
Multiple Bioactivation of Chloroform: A Comparison Between Man and Experimental Animals....Pages 665-667
CCl 4 -Induced Cytochrome P-450 Loss and Lipid Peroxidation in Rat Liver Slices....Pages 669-674
Alteration of Benzo(A)Pyrene-DNA Adduct Formation by Rats Exposed to Simple Mixtures....Pages 675-679
Comparison of the Toxicity of Naphthalene and Naphthalene-1,2-Dihydrodiol (DIOL)....Pages 681-684
Selective Binding of Acetaminophen (APAP) to Liver Proteins in Mice and Men....Pages 685-688
Post-Treatment Protection with Piperonyl Butoxide Against Acetaminophen Hepatotoxicity is Associated with Changes in Selective but Not Total Covalent Binding....Pages 689-692
Covalent Binding of a Halothane Metabolite and Neoantigen Production in Guinea Pig Liver Slices....Pages 693-697
Extensive Alteration of Genomic DNA and Rise in Nuclear Ca 2+ in Vivo Early after Hepatotoxic Acetaminophen Overdose in Mice....Pages 699-705
The Possible Role of Glutathione on the Hepatotoxic Effect of Papaverine Hydrochloride in Vitro ....Pages 707-709
 In Vivo and in Vitro Evidence for in Situ Activation and Selective Covalent Binding of Acetaminophen (APAP) in Mouse Kidney....Pages 711-716
Metabolism of Dichlorobenzenes in Organ Cultured Liver Slices....Pages 717-723
Inhibition of Protein Synthesis and Secretion by Volatile Anesthetics in Guinea Pig Liver Slices....Pages 725-730
Dichlorobenzene Hepatotoxicity Strain Differences and Structure Activity Relationships....Pages 731-734
The Use of 19 F NMR in the Study of Protein Alkylation by Fluorinated Reactive Intermediates....Pages 735-738
S-Ethylthiotrifluoroacetate Enhancement of the Immune Response to Halothane in the Guinea Pig....Pages 739-744
Bone Marrow DNA Adducts and Bone Marrow Cellularity Following Treatment with Benzene Metabolites in Vivo ....Pages 745-748
The Role of γ-Glutamyl Transpeptidase in Hydroquinone-Glutathione Conjugate Mediated Nephrotoxicity....Pages 749-751
Cytochrome P450IIE1 Metabolism of Pyridines: Evidence for Production of a Reactive Intermediate which Exhibits Redox-Cycling Activity and Causes DNA Damage....Pages 753-758
Morphological Cell Transformation and DNA Adduction by Benz(J)Aceanthrylene and its Presumptive Reactive Metabolites in C3H10T1/2CL8 Cells....Pages 759-762
Covalent Binding of Oxidative Biotransformation Reactive Intermediates to Protein Influences Halothane-Associated Hepatotoxicity in Guinea Pigs....Pages 763-766
The Nephrotoxicity of 2,5-Dichloro-3-(Glutathion-S-YL)-1,4-Benzo-Quinone, and 2,5,6-Trichloro-3-(Glutathion-S-YL)-1,4-Benzoquinone is Potentiated by Ascorbic Acid and AT-125....Pages 767-769
Generation of Free Radicals Results in Increased Rates of Protein Degradation in Human Erythrocytes....Pages 771-776
Free Radicals Generated in Ethanol Metabolism May Be Responsible for Tumor Promoting Effects of Ethanol....Pages 777-783
Composition of Hepatic Lipids after Ethanol, Cod Liver Oil and Vitamin E Feeding in Rats....Pages 785-788
Dietary Polyunsaturated Fatty Acid Promote Peroxidation and its Possible Role in the Promotion of Cancer....Pages 789-791
Chiral Epoxides, their Enantioselective Reactivity Towards Nucleic Acids, and a First Outline of a Quantum Chemical Structure-Reactivity Calculation....Pages 793-799
Comparison of 8-Hydroxydeoxyguanosine and 5-Hydroxymethyluracil as Products of Oxidative DNA Damage....Pages 801-803
Modulation of Aortic Smooth Muscle Cell Prolifertion by Dinitrotoluene....Pages 805-808
Reactive Potential of Diethylstilbestrol Reactive Metabolites Towards Cellular Nuclear Proteins: Implications for Estrogen*Induced Carcinogenesis....Pages 809-812
Biochemical and Morphologic Response of Nasal Epithelia to Hyperoxia....Pages 813-816
Membrane Stabilization as a Fundamental Event in the Mechanism of Chemoprotection Against Chemical Intoxication....Pages 817-819
Biochemical Effects and Toxicity of Mitoxantrone in Cultured Heart Cells....Pages 821-825
Evidence for the Induction of an Oxidative Stress in Rat Hepatic Mitochondria by 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (TCDD)....Pages 827-831
Antioxidation Potential of Indole Compounds — Structure Activity Studies....Pages 833-836
Measurement of Styrene-Oxide Cysteine Adducts in Hemoglobin by Selective Catalytic Reduction....Pages 837-841
Studies on Biochemical Determinants of Quinone-Induced Toxicity in Primary Murine Bone Marrow Stromal Cells....Pages 843-846
Selective Alteration of Cytokeratin Intermediate Filament by Cyclosporine A is a Lethal Toxicity in PTK2 Cell Cultures....Pages 847-851
Rat Hepatic DNA Damage Induced by 1,2,3-Trichloropropane....Pages 853-855
Oxidation of Reduced Porphyrins by the Mitochondrial Electron Transport Chain: Stimulation by Iron and Potential Role of Reactive Oxygen Species....Pages 857-862
Future Research Needs for the Application of Mechanistic Data to Risk Assessment....Pages 863-868
Back Matter....Pages 869-894