Ebook: Molecular Aspects of Oxidative Drug Metabolizing Enzymes: Their Significance in Environmental Toxicology, Chemical Carcinogenesis and Health

Presented here are recent advances in biochemical, toxicological, and regulatory aspects of oxidative drug metabolizing enzymes. Mainly cytochrome P450-dependent and flavin-containing monooxygenases (FMO) are covered. Moreover, the book deals with genotoxicity studies and toxicological interactions of environmental chemicals and mechanisms of mutagenicity and tumor formation. The construction of genetically engineered mammalian cells for the production of a specific P450 isozyme and the application of these cell lines in drug metabolism, mutagenicity and toxicity studies are described in detail. Further, insight is provided into how a number of aquatic species cope with pollutants and their genotoxicity.

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Presented here are recent advances in biochemical, toxicological, and regulatory aspects of oxidative drug metabolizing enzymes. Mainly cytochrome P450-dependent and flavin-containing monooxygenases (FMO) are covered. Moreover, the book deals with genotoxicity studies and toxicological interactions of environmental chemicals and mechanisms of mutagenicity and tumor formation. The construction of genetically engineered mammalian cells for the production of a specific P450 isozyme and the application of these cell lines in drug metabolism, mutagenicity and toxicity studies are described in detail. Further, insight is provided into how a number of aquatic species cope with pollutants and their genotoxicity.

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Presented here are recent advances in biochemical, toxicological, and regulatory aspects of oxidative drug metabolizing enzymes. Mainly cytochrome P450-dependent and flavin-containing monooxygenases (FMO) are covered. Moreover, the book deals with genotoxicity studies and toxicological interactions of environmental chemicals and mechanisms of mutagenicity and tumor formation. The construction of genetically engineered mammalian cells for the production of a specific P450 isozyme and the application of these cell lines in drug metabolism, mutagenicity and toxicity studies are described in detail. Further, insight is provided into how a number of aquatic species cope with pollutants and their genotoxicity.
Content:
Front Matter....Pages I-IX
Introduction to Cytochrome P450....Pages 1-19
General Aspects of NADPH Cytochrome P450 Reductase and Cytochrome b5....Pages 21-45
Interaction Between Cytochrome P450 and Reductase....Pages 47-63
Molecular Biology of Cytochrome P-450: Evolution, Structure and Regulation....Pages 65-85
The Role of Nuclear Receptors in the Regulation of P450s and Other Genes by Peroxisome Proliferators....Pages 87-103
Mapping Determinants of the Substrate Specificities of P450s by Site-Directed Mutagenesis....Pages 105-134
Diversity and Regulation of Cytochromes P450 in Aquatic Species....Pages 135-158
Cytochrome P450 Expression in Rainbow Trout: An Overview....Pages 159-180
Molecular Aspects of Cytochrome P450 2E1 and Its Roles in Chemical Toxicity....Pages 181-192
Problems Associated with Assessment of the Contribution of Individual Forms of Cytochrome P450 to the Metabolism of Xenobiotics....Pages 193-207
Emergence of the Flavin-Containing Monooxygenase Gene Family: Molecular Biology, Structure, and Function....Pages 209-224
Flavin-Containing Monooxygenases: Substrate Specificity and Complex Metabolic Pathways....Pages 225-235
Developmental Regulation of Biotransformation of Drugs and other Xenobiotics....Pages 237-248
Modulation of Xenobiotic Metabolism and Toxicity by Dietary Chemical....Pages 249-259
Mechanisms of Mutagenicity and Tumour Formation....Pages 261-302
Genotoxicity assays....Pages 303-396
Use of Mechanistic Information for Adequate Metabolic Design of Genotoxicity Studies and Toxicological Interactions of Drugs and Environmental Chemicals....Pages 397-409
Significance of Posttranslational Modification of Drug Metabolizing Enzymes by Phosphorylation for the Control of Carcinogenic Metabolites....Pages 411-427
The Construction of Cell Cultures Genetically Engineered for Metabolic Competence towards Xenobiotics....Pages 429-454
In Vitro Systems as Analytical Tools for Understanding and Predicting Drug Metabolism In Vivo....Pages 455-460
The Role of Oxidative Enzymes in the Metabolism and Toxicity of Pesticides....Pages 461-478
Metabolism of Xenobiotic Proestrogens and Estrogens by Cytochrome P450....Pages 479-489
Metabolism of Antiestrogenic Anti-Cancer Agents by Cytochromne P450 and Flavin-Containing Monooxygenases. Mechanism of Action Involving Metabolites....Pages 491-502
Therapeutic Agents and Cytochrome P450....Pages 503-513
Drug Metabolism, Lipid Peroxidation and Glutathione....Pages 515-532
Health Environment of Altai Territory and Monooxygenase and Conjugating Activities in Placentae of Newborn....Pages 533-548
Monooxygenase Measurements as Indicators of Pollution in the Field....Pages 549-565
Biochemical and Genotoxicological Monitoring of Ecosystems with Special Reference to Lake Baikal and Northern Black Sea....Pages 567-589
Relating Biochemical Responses to “Higher Order” Effects....Pages 591-603
Back Matter....Pages 605-620

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Presented here are recent advances in biochemical, toxicological, and regulatory aspects of oxidative drug metabolizing enzymes. Mainly cytochrome P450-dependent and flavin-containing monooxygenases (FMO) are covered. Moreover, the book deals with genotoxicity studies and toxicological interactions of environmental chemicals and mechanisms of mutagenicity and tumor formation. The construction of genetically engineered mammalian cells for the production of a specific P450 isozyme and the application of these cell lines in drug metabolism, mutagenicity and toxicity studies are described in detail. Further, insight is provided into how a number of aquatic species cope with pollutants and their genotoxicity.
Content:
Front Matter....Pages I-IX
Introduction to Cytochrome P450....Pages 1-19
General Aspects of NADPH Cytochrome P450 Reductase and Cytochrome b5....Pages 21-45
Interaction Between Cytochrome P450 and Reductase....Pages 47-63
Molecular Biology of Cytochrome P-450: Evolution, Structure and Regulation....Pages 65-85
The Role of Nuclear Receptors in the Regulation of P450s and Other Genes by Peroxisome Proliferators....Pages 87-103
Mapping Determinants of the Substrate Specificities of P450s by Site-Directed Mutagenesis....Pages 105-134
Diversity and Regulation of Cytochromes P450 in Aquatic Species....Pages 135-158
Cytochrome P450 Expression in Rainbow Trout: An Overview....Pages 159-180
Molecular Aspects of Cytochrome P450 2E1 and Its Roles in Chemical Toxicity....Pages 181-192
Problems Associated with Assessment of the Contribution of Individual Forms of Cytochrome P450 to the Metabolism of Xenobiotics....Pages 193-207
Emergence of the Flavin-Containing Monooxygenase Gene Family: Molecular Biology, Structure, and Function....Pages 209-224
Flavin-Containing Monooxygenases: Substrate Specificity and Complex Metabolic Pathways....Pages 225-235
Developmental Regulation of Biotransformation of Drugs and other Xenobiotics....Pages 237-248
Modulation of Xenobiotic Metabolism and Toxicity by Dietary Chemical....Pages 249-259
Mechanisms of Mutagenicity and Tumour Formation....Pages 261-302
Genotoxicity assays....Pages 303-396
Use of Mechanistic Information for Adequate Metabolic Design of Genotoxicity Studies and Toxicological Interactions of Drugs and Environmental Chemicals....Pages 397-409
Significance of Posttranslational Modification of Drug Metabolizing Enzymes by Phosphorylation for the Control of Carcinogenic Metabolites....Pages 411-427
The Construction of Cell Cultures Genetically Engineered for Metabolic Competence towards Xenobiotics....Pages 429-454
In Vitro Systems as Analytical Tools for Understanding and Predicting Drug Metabolism In Vivo....Pages 455-460
The Role of Oxidative Enzymes in the Metabolism and Toxicity of Pesticides....Pages 461-478
Metabolism of Xenobiotic Proestrogens and Estrogens by Cytochrome P450....Pages 479-489
Metabolism of Antiestrogenic Anti-Cancer Agents by Cytochromne P450 and Flavin-Containing Monooxygenases. Mechanism of Action Involving Metabolites....Pages 491-502
Therapeutic Agents and Cytochrome P450....Pages 503-513
Drug Metabolism, Lipid Peroxidation and Glutathione....Pages 515-532
Health Environment of Altai Territory and Monooxygenase and Conjugating Activities in Placentae of Newborn....Pages 533-548
Monooxygenase Measurements as Indicators of Pollution in the Field....Pages 549-565
Biochemical and Genotoxicological Monitoring of Ecosystems with Special Reference to Lake Baikal and Northern Black Sea....Pages 567-589
Relating Biochemical Responses to “Higher Order” Effects....Pages 591-603
Back Matter....Pages 605-620
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