Biological Reactive Intermediates III: Mechanisms of Action in Animal Models and Human Disease

ISBN-13: 9781468451368 / Angielski / Miękka / 2013 / 1059 str.

James J. Kocsis; David J. Jollow; Charlotte M. Witmer

Opis

This volume contains the proceedings of the third in a series of conferences entitled, The International Symposium on Biological Reactive Intermediates. The first was held at the University of Turku in Finland, in 1975, the second at the University of Surrey in the United Kingdom, in 1980 and the most recent at the University of Maryland in the United States, in 1985. The significance of these conferences has been emphasized by the rapid growth of mechanistic toxicology over the last decade. These conferences were initially stimulated by the attempt to uncover the significance behind the observations that the toxicity of carcinogenic responses produced by many chemicals was associated with the observation that their metabolism led to the formation of chemcially reactive electrophiles which covalently bound to nucleophilic sites in cells such as proteins, nucleic acid or fats. Recently, newer concepts have arisen which have necessitated the expansion of subjects covered by the conference. For example, the application of newer knowledge of the role of active oxygen species in reactive metabolite formation, the concept of suicide substrates, examination of the function of glutathione in cells, application of immunological techniques and molecular biological probes to the solution of toxicological problems all had an impact on the study of the biological reactive intermediates.

Spis treści

Years with Elizabeth and James Miller: In Appreciation.- I. Chemistry and Biology of Biological Reactive Intermediates.- Reactivity and Tumorigenicity of Bay-Region Diol Epoxides Derived From Polycyclic Aromatic Hydrocarbons.- Chemistry of Covalent Binding: Studies with Bromobenzene and Thiobenzamide.- Role of Thiols in Protection Against Biological Reactive Intermediates.- Role of Parenchymal Versus Non-Parenchymal Cells in the Control of Biologically Reactive Intermediates.- Significance of Covalent Binding of Chemically Reactive Metabolites of Foreign Compounds to Proteins and Lipids.- II. Biology of Cytochrome P-450 and Related Aspects of the Mixed Function Oxidase.- Structure and Function of Cytochrome P-450.- Antibodies As Probes of Cytochrome P450 Isozymes.- Age and Sex Differences in Constitutive Forms of Cytochrome P-450 of Rat Liver Microsomes.- Identification of Intratissue Sites for Xenobiotic Activation and Detoxication.- Monoclonal Antibody-Directed Analysis of Cytochrome P-450.- III. Suicide Substrates of Cytochrome P-450.- Drug Interactions with Macrolide Antibodies: Specificity of Pseudo-Suicide of Inhibition and Induction of Cytochrome P-450.- Isomeric Composition of N-Alkylated Protoporplhyrins Produced by Substituted Dihydropyridines In Vivo and In Vitro.- IV. Characterization and Toxicological Significance of Phase II Enzymes.- UDP-Glucuronyltransferases and Their Toxicological Significance.- Expression and Sequence Analysis of Rat Liver Glutathione S-Transferase Genes.- Rat Cytosolic Epoxide Hydrolase.- Short Communications.- Multiplicity of Cytochrome P-450 in Morris Hepatoma.- The Metabolism of Benzene and Phenol by a Reconstituted Purified Phenobarbital-Induced Rat Liver Mixed Function Oxidase System.- Comparison of The Metabolism of Benzene and its Metabolite Phenol in Rat Liver Microsomes.- Further Evidence for a Role of Isozymes of P450 in the Metabolism and Toxicity of Carbon Disulfide (CS2).- Effect of a Suicide Substrate on the Metabolism of Steroids and Xenobiotics and on Cytochrome P-450 Apoproteins.- Activation of Cytochrome P-450 Heme In Vivo.- The FAD-Containing Monooxygenase of Lung and Liver Tissue From Rabbit, Mouse and Pig: Species and Tissue Differences.- Oxygen Radical Formation During Redox Cycling of Bleomycin-Fe(III) Catalyzed by NADPH-Cytochrome P-450 Reductase of Liver Microsomes and Nuclei.- Superoxide Dismutase Modification and Genotoxicity of Transition-Metal Ion Chelators.- Toxicologic Implications of the Iron-Dependent Activation of Bleomycin A2 By Mouse Lung Microsomes.- The Peroxidative Activation of Butylated Hydroxytoluene to BHT-Quinone Methide and Stilbenequinone.- Activation of Xenobiotics by Human Polymorphonuclear Leukocytes via Reactive Oxygen-Dependent Reactions.- Metabolism of Diehtylstilbestrol by Horseradish Peroxidase and Prostaglandin Suynthase-Evidence For A Free Radical Intermediate.- Thiyl Radicals--Their Generation and Further Reactions.- Mechanism of the Cytochrome P-450 Catalyzed Isomerization of Hydroperoxides.- Indole-3-Carbinol Inhibits Lipid Peroxidation in Cell-Free Systems.- Glutathione Peroxidase and Reactive Oxygen Species in TCDD-Induced Lipid Peroxidation.- Activation of Nitrosamines to Mutagens by Rat and Rabbit Nasal, Lung and Liver S-9 Homogenates.- Structure of the Adduct of Glutathione and Activated 3-Mathylindole.- Studies on the Mechanisms of S-Cysteine Conjugate Metabolism and Toxicity in Rat Liver, Kidney and Cell Culture Model.- Formation of Identification of Naphthoquinone Glutathione Conjugates Following Microsomal Metabolism of 1-Naphthol.- The Formation of N-Glucuronides Catalyzed by Purified Hepatic 17 ? -Hydroxysteroid and 3? -Hydroxysteroid UDP-Glucuronyltransferase.- Improved Method For Determination of Cellular Thiols, Disulfides and Protein Mixed Disulfides using HPLC with Electrochemical Detection.- Arylsulfotransferase IV Catalyzed Sulfation of 1-Naphthalenemethanol.- Activated Phase II Metabolites: Comparison of Alkylation by 1-0-Acyl Glucuronides and Acyl Sulfates.- Reactions of Oxaprozin-1-0-Acyl Glucuronide in Solutions of Human Plasma and Albumin.- V. Role of Sulfur in Metabolic Activation and Detoxication.- Nephrotoxic Amino Acid and Glutathione S-Conjugates: Formation and Renal Activation.- The Role of Glutathione in the Toxicity of Xenobiotic Compounds: Metabolic Activation of 1,2-Dibromoethane By Glutathione.- A Comparison of the Alkylating Capabilities of the Cysteinyl and Glutationyl Conjugates of 1,2-Dichloroethane.- Covalent Reactions in the Toxicity of SO2 and Sulfite.- VI. Active Oxygen and Triol Oxidations.- One- And Two-Electron Oxidation of Reduced Glutathione By Peroxidases.- Reactive Oxygen Species Formed In Vitro and in Cells: Role of Thiols (GSH) Model Studies with Xanthine Oxidase and Horseradish Peroxidase.- Active Oxygen and Toxicity.- VII. Reactive Metabolites of Nitrogenous Compounds.- Studies on the Mechanism of Activation and the Mutagenicity of Ronidazole, a 5-Nitroimidazole.- Carcinogen-DNA Adduct Formation as a Predictor of Metabolic Activation Pathways and Reactive Intermediates in Benzidine Carcinogenesis.- Purification, Properties and Function of N-Hydroxyarylamine 0-Acetyltransferase.- Metabolism and Carcinogenicity of Nitrotoluenes.- Hydroxylamines and Hemolytic Anemia.- Special Presentation.- Electrophilic Sulfuric Acid Ester Metabolites as Ultimate Carcinogens.- VIII. Toxicity of Biological Reactive Intermediates.- Biological Reactive Intermediates of Mycotoxins.- Biological Reactive Intermediates of Pyrrolizidine Alkaloids.- Mutagens and Carcinogens Formed During Cooking.- Quinone Imines as Biological Reactive Intermediates.- IX. Biological Reactive Intermediates and the Immune System.- The Role of Reactive Intermediates in Sulfhydryl-Dependent Immunotoxicity: Interference with Microtubule Assembly and MicrotubuleDependent Cell Function.- Investigation of the Immunological Basis of Halothane-Induced Hepatotoxicity.- Inhibition of RNA Synthesis in Mouse Macrophages and Lymphocytes by Benzene and its Metabolites.- Short Communications.- p-Nitrosophenetole: A Reactive Intermediate of Phenacetin that Binds To Protein.- Mechanism of Fasting-Induced Suppression of Acetaminophen Glucuronidation in The Rat.- Effect of Diethyl Ether on the Bioactivation, Detoxification and Hepatotoxicity of Acetaminophen in vitro and in vivo.- Piperonyl Butoxide Reduces Salicylate-Induced Nephrotoxicity and Covalent Binding in Male Rats.- Cross-Linking of Protein Molecules by the Reactive Metabolite of Acetaminophen, N-Acetyl-p-Benzoquinone Imine, and Related Quinoid Compounds.- Acetaminophen as a Cosubstrate and Inhibitor of Prostaglandin H Synthetase.- The Fate of 4-Cyanoacetanilide in Rats and Mice: The Mechanism Of Formation Of A Novel Electrophilic Metabolite.- Mechanistic Studies of Acetamide Hepatocarcinogenicity.- Reactions of Glutathione with Oxidative Intermediates of Acetaminophen.- Flavin-Containing Monooxygenase Activity in Human Liver Microsomes.- S9-Dependent Activation of 1-Nitropyrene and 3-Nitrofluoranthene in Bacterial Mutagenicity Assays.- Formation of a Ring-Opened Product from Benzene in a Hydroxyl Radical Generating System.- H-2 Modulation of Lauryl Hydrocarbon Hydroxylase Induction and the Mutagenicity of Benzo(a)Pyrene after 3-Methylcholanthrene Treatment.- Stereoselectivity of Rat Liver Cytochrome P-450 Isozymes: Direct Determination of Enantiomeric Composition of K-Region Epoxides Formed in the Metabolism of Benz(a)anthracene and 7,12-Dimethylbenz(a)anthracene.- Induction of Unscheduled DNA Synthesis in Human Mononuclear Leukocytes by Oxidative Stress.- Deoxyguanosine Adducts Formed from Benzoquinone and Hydroquinone.- 3-Hydroxy-Trans-7,8-Dihydro-7,8-Dihydroxy-Benzo(a)Pyrene, a Metabolite of 3-Hydroxybenzo(a)pyrene.- Time Course of The Effect of 4-Hydroperoxycyclophosphamide On Limb Differentiation in vitro.- Hepatic Pathological Changes due to Hydroxyalkenals.- Clofibrate Selectively Induces Azoreduction of Dimethylaminoazobenzene (DAB) by Rat Liver Microsomes.- Intracellular Dissipative Structures (IDS) as Ultimate Targets of Chemical Cytotoxicity.- Helenalin: Mechanism of Toxic Action.- Evidence for Stereoselective Production of Phenytoin (5,5-Diphenylhydantoin) Arene Oxides In Man.- Tissue Distribution and Covalent Binding of [14C]1,1-Dichloroethylene in Mice: in vivo and in vitro Studies.- Inhibition of Respiration in Rabbit Proximal Tubules by Bromophenols and 2-Bromohydroquinone.- In vitro Covalent Binding of 14C-Mibolerone to Rat Liver Microsomes.- Chemistry of Metabolites of Thioureas.- Conversion of Phenytoin to Reactive Metabolites in Rat Liver Microsomes.- Comparison of N-Methylformamide-Induced Hepatotoxicity and Metabolism in Rats and Mice.- Epoxidation of 1,3-Butadiene in Liver and Lung Tissue of Mouse, Rat, Monkey and Man.- Enzyme Catalysed Cleavage of the N-N Bond of N-Nitrosamines.- Use of the Chemiluminigenic Probes Luminol and Lucigenin for the Detection of Active Oxygen Species in Hepatic Microsomes and in Intact Hepatocytes.- X. Implications of Renobiotic Metabolism for Human Disease.- Altered Expression of Oncogenes in Mouse Epidermis Following Exposure To Benzo(A)Pyrene Diol Epoxides.- Acetaminophen Toxicity in Isolated Hepatocytes.- Mechanism of Organ Specificity in Nitrosamine Carcinogenesis.- Biological Reactive Metabolites in Human Toxicity.- Metabolic Host Factors as Modifiers of Reactive Intermediates Possibly Involved in Human Cancer.- Closing Remarks.