Molecular Aspects of Oxidative Drug Metabolizing Enzymes

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.

Proceedings of the NATO Advanced Study Institute on molecular aspects of drug metabolizing enzymes, held in Kusadasi, Aydin-Turkey, June 20-July 2, 1993

to Cytochrome P450.- General Aspects of NADPH Cytochrome P450 Reductase and Cytochrome b5.- Interaction Between Cytochrome P450 and Reductase.- Molecular Biology of Cytochrome P450: Evolution, Structure and Regulation.- The Role of Nuclear Receptors in the Regulation of P450s and Other Genes by Peroxisome Proliferators.- Mapping Determinants of the Substrate Specificities of P450s by Site-Directed Mutagenesis.- Diversity and Regulation of Cytochromes P450 in Aquatic Species.- Cytochrome P450 Expression in Rainbow Trout: An Overview.- Molecular Aspects of Cytochrome P450 2E1 and Its Roles in Chemical Toxicity.- Problems Associated with Assessment of the Contribution of Individual Forms of Cytochrome P450 to the Metabolism of Xenobiotics.- Emergence of the Flavin-Containing Monooxygenase Gene Family: Molecular Biology, Structure, and Function.- Flavin-Containing Monooxygenases: Substrate Specificity and Complex Metabolic Pathways.- Developmental Regulation of Biotransformation of Drugs and Other Xenobiotics.- Modulation of Xenobiotic Metabolism and Toxicity by Dietary Chemical.- Mechanisms of Mutagenicity and Tumour Formation.- Genotoxicity Assays.- Use of Mechanistic Information for Adequate Metabolic Design of Genotoxicity Studies and Toxicological Interactions of Drugs and Environmental Chemicals.- Significance of Posttranslational Modification of Drug Metabolizing Enzymes by Phosphorylation for the Control of Carcinogenic Metabolites.- The Construction of Cell Cultures Genetically Engineered for Metabolic Competence towards Xenobiotics.- In Vitro Systems as Analytical Tools for Understanding and Predicting Drug Metabolism In Vivo.- The Role of Oxidative Enzymes in the Metabolism and Toxicity of Pesticides.- Metabolism of Xenobiotic Proestrogens and Estrogens by Cytochrome P450.- Metabolism of Antiestrogenic Anti-Cancer Agents by Cytochrome P450 and Flavin-Containing Monooxygenases. Mechanism of Action Involving Metabolites.- Therapeutic Agents and Cytochrome P450.- Drug Metabolism, Lipid Peroxidation and Glutathione.- Health Environment of Altai Territory and Monooxygenase and Conjugating Activities in Placentae of Newborn.- Monooxygenase Measurements as Indicators of Pollution in the Field.- Biochemical and Genotoxicological Monitoring of Ecosystems with Special Reference to Lake Baikal and Northern Black Sea.- Relating Biochemical Responses to "Higher Order" Effects.- List of Invited Contributors.