Biological Reactive Intermediates

1. Front Matter

   Pages i-xi

   PDF

2. Reactive Intermediates in Toxicology and Carcinogenesis: Role of Covalent Binding

   1. Front Matter

      Pages 1-1

      PDF

   2. Introduction to the Concept of Reactive Intermediates

      • R. T. Williams

      Pages 3-5

   3. The Concept of Reactive Electrophilic Metabolites in Chemical Carcinogenesis: Recent Results with Aromatic Amines, Safrole, and Aflatoxin B1

      • James A. Miller, Elizabeth C. Miller

      Pages 6-24

   4. Kinetics of Reactive Metabolites and Covalent Binding in Vivo and in Vitro

      • James R. Gillette

      Pages 25-41

   5. Biochemical Aspects of Toxic Metabolites: Formation, Detoxication, and Covalent Binding

      • David J. Jollow, Carole Smith

      Pages 42-59

   6. Discussion

      • David J. Jollow, James J. Kocsis, Robert Snyder, Harri Vainio, Jussi Saukkonen, Charlotte Witmer et al.

      Pages 60-61

3. Formation of Reactive Intermediates

   1. Front Matter

      Pages 63-63

      PDF

   2. Mechanism of Microsomal Monooxygenases and Drug Toxicity

      • Volker Ullrich

      Pages 65-80

   3. Discussion

      • David J. Jollow, James J. Kocsis, Robert Snyder, Harri Vainio, Jussi Saukkonen, Charlotte Witmer et al.

      Pages 81-82

   4. Aryl Hydrocarbon Hydroxylase: Induction

      • John B. Schenkman, Kathy M. Robie, Ingela Jansson

      Pages 83-95

   5. Discussion

      • David J. Jollow, James J. Kocsis, Robert Snyder, Harri Vainio, Jussi Saukkonen, Charlotte Witmer et al.

      Pages 96-97

   6. Benzo[a]pyrene Metabolism: Enzymatic and Liquid Chromatographic Analysis and Application to Human Liver, Lymphocytes, and Monocytes

      • Harry V. Gelboin, James Selkirk, Takao Okuda, Nobuo Nemoto, Shen K. Yang, Friedrich J. Wiebel et al.

      Pages 98-123

   7. Discussion

      • David J. Jollow, James J. Kocsis, Robert Snyder, Harri Vainio, Jussi Saukkonen, Charlotte Witmer et al.

      Pages 124-124

   8. Genetic Differences in Benzo[a]pyrene Carcinogenic Index in Vivo and in Mouse Cytochrome P₁ 450-Mediated Benzo[a]pyrene Metabolite Binding to DNA in Vitro

      • Daniel W. Nebert, Alan R. Boobis, Haruhiko Yagi, Donald M. Jerina, Richard E. Kouri

      Pages 125-145

   9. Discussion

      • David J. Jollow, James J. Kocsis, Robert Snyder, Harri Vainio, Jussi Saukkonen, Charlotte Witmer et al.

      Pages 146-147

   10. Formation of Toxic Intermediates in Fetal Tissues

       • Olavi Pelkonen

       Pages 148-159

   11. Discussion

       • David J. Jollow, James J. Kocsis, Robert Snyder, Harri Vainio, Jussi Saukkonen, Charlotte Witmer et al.

       Pages 160-161

   12. The Possible Role of Trout Liver Aryl Hydrocarbon Hydroxylase in Activating Aromatic Polycyclic Carcinogens

       • Jorma T. Ahokas, Olavi Pelkonen, Niilo T. Kärki

       Pages 162-166

   13. Metabolic Activation of Methyldopa by Cytochrome P450-Generated Superoxide Anion

       • E. Dybing, J. R. Mitchell, S. D. Nelson, J. R. Gillette

       Pages 167-172

The concept that detoxication is the inevitable result of biotransformation of xenobiotic compounds by mammalian systems has undergone modification since it was first described. Indeed, despite the fact that R. T. Williams popularized the notion, he was among the first to caution that it was not possible to predict the biological activities of the resulting metabolites. It has become increasingly apparent in recent years that not only do many metabolites of drugs and other chemicals display biological activity but also in many instances these metabolites play an important role in initiating several forms of cancer and are the cause of a variety of types of toxicity. Thus it seems appropriate to collect in one volume a series of reports outlining advances in the study of the formation of chemically active intermediary metabolic products of chemicals, mechanisms of toxicity or carcinogenesis, and pathways for true detoxication of these chemicals. The work of R. T. Williams, beginning in the late 1920s and early 1930s, marked the first concerted effort to understand the biotransformation of foreign chemicals in animals. He investigated the metabolic pathway of numerous compounds in a wide variety of animal species while training large numbers of our colleagues who have been responsible for further advances in biochemistry, pharmacology, and toxicology. Another pioneer in the study of drug metabo­ lism, B. B.

• Activation
• DNA
• Lipid
• Nucleotide
• Oxidation
• animals
• biochemistry
• chemistry
• enzymes
• metabolism
• oncogene
• pharmacology
• synthesis
• toxicity
• toxicology

• Medical University of South Carolina, Charleston, USA

  David J. Jollow, Thomas Walle

• Thomas Jefferson University, Philadelphia, USA

  James J. Kocsis, Robert Snyder, Jussi Saukkonen, Charlotte Witmer

• Institute of Occupational Health, Helsinki, Finland

  Harri Vainio

Policies and ethics