Cancer. A Comprehensive Treatise

This series of books attempts to present, in a comprehensive manner, the field of oncology divided into three major areas; etiology, biology, and therapy. These books should serve as landmarks in the rapidly expanding experimental and clinical "universe" of this field. To some, they will be introductory; to others, a summary; for all, critical comments on the futuI'e of research. In l'ecognition of the difficulties inherent in attempting to pause and reflect while experimental data emerge with ever-increasing rapidity, the presentations take the form of overviews rather than reviews. Where possible, an historical perspective on observations and experimentation which led to our present understanding is presented, the state of the art in technique and approach is reviewed, and the gaps in knowledge and in technique are indicated. The aim throughout is integration-using the findings from one approach for comparison with others. The tremendous expansion of interest in oncology as a medical-biological discipline stimulated the publication of these volumes. This expansion, well warranted in terms of the impact of oncology on human morbidity, has been characterized by at least three phenomena. First, there has been an enormous increase in money and manpower devoted to the investigation and treatment of malignancy. That the research has become more and more "directed" or program-oriented signals the interest of those beyond the scientific community in the management of the eHort. Second, increasing numbers of students are entering the field of oncology as their major training program.

Inhalt

General Concepts.- Cytogenetics.- 1. Introduction.- 2. Human Leukemias.- 2.1. Chronic Granulocytic Leukemia and the Philadelphia-Chromosome.- 2.2. Other Myeloproliferative Disorders and "Preleukemia".- 2.3. Acute Leukemias.- 2.4. Lymphoproliferative Disorders.- 3. Human Solid Tumors.- 3.1. Malignant Tumors.- 3.2. Benign and Precancerous Lesions.- 4. Animal Tumors.- 4.1. Viral Tumors and Transformed Cells.- 4.2. Solid Tumors and Clonal Evolution.- 5. Chromosome Breakage and Cancer.- 5.1. Genetic Disorders.- 5.2. Exogeneous Agents-Radiation, Chemicals, Viruses.- 6. Conclusions and Speculations.- 7. References.- Genetics: Animal Tumors.- 1. Introduction.- 2. Speciation and Tumor Formation.- 2.1. Invertebrates.- 2.2. Vertebrates.- 3. Hybridization and Tumor Formation.- 3.1. Hybridization of Species.- 3.2. Hybridization of Strains.- 4. Inbreeding and Occurrence of Tumors.- 4.1. Development of Inbred Strains.- 4.2. Tumor Characteristics of Inbred Strains of Mice.- 4.3. Role of Inbred Strains and Their Hybrids in Cancer Research.- 5. Genetics of Spontaneous Tumors.- 5.1. The Threshold Concept in the Inheritance of Cancer.- 5.2. The Somatic Mutation Hypothesis.- 6. Genetics of Chemically Induced Tumors.- 6.1. Pulmonary Tumors in Mice.- 6.2. Subcutaneous Sarcomas in Mice.- 6.3. Selection of Appropriate Strain for Testing Carcinogens.- 7. Genetics of Hormonally Induced Tumors.- 7.1. Mammary Tumors.- 7.2. Hypophyseal Tumors.- 7.3. Adrenocortical Tumors.- 8. Genetics of Virally Induced Tumors.- 8.1. Inheritance of Susceptibility to the Mammary Tumor Virus.- 8.2. Inheritance of Susceptibility to Leukemia.- 8.3. GeneticTransmissionof Tumor Viruses.- 9. References.- Genetic Influences in Human Tumors.- 1. Introduction.- 2. Genetic States Predisposing to Cancer.- 2.1. Chromosomal Disorders.- 2.2. Mendelian Conditions.- 3. Dominantly Inherited Tumors.- 3.1. Tumor Syndromes.- 3.2. Specific Tumors.- 4. A Mutation Model for Human Cancer.- 4.1. Initiation in Two or More Steps.- 4.2. Genetic Consequences.- 4.3. Role of Environmental Carcinogens.- 5. Conclusions.- 6. References.- Hormones as Etiological Agents in Neoplasia.- 1. General Considerations.- 1.1. Historical.- 1.2. Nomenclature and Abbreviations.- 1.3. Neoplasia: Basic Defect and Types.- 1.4. Homeostasis (Cybernetics) and Neoplasia.- 1.5. Tumorigenesis by Hormonal Derangement.- 2. The Four Levels of Communications.- 2.1. Neurohypothalamic Areas and Neoplasia.- 2.2. Cell Type of the Adenohypophysis and Their Neoplasms.- 2.3. Neoplasia in Peripheral Endocrine-Related Organs.- 3. Detection of Hormonal Activity.- 3.1. General Considerations.- 3.2. Detection and Quantitation of Hormones.- 3.3. Steroid vs. Protein Hormones: Their Receptors and Translation of their Messages.- 4. Ectopic Hormones.- 5. Sequential Events: Multiglandular Syndromes.- 5.1. Neonatal Ovariectony.- 5.2. Thyroidal Carcinogenesis.- 5.3. Multiglandular Diseases.- 6. Problems and Prospects.- 6.1. The Basic Change in Neoplasia.- 6.2. Carcinogenesis without Extrinsic Carcinogens.- 6.3. Relation of Neoplasia to Aging.- 6.4. Prospects.- 7. References.- Immunocompetence and Malignancy.- 1. Introduction.- 2. Deliberate Immunosuppression and Malignancy in Experimental Animals.- 2.1. Immunosuppression and Infection with Oncogenic Viruses.- 2.2. Effects of Immunosuppression on Oncogenesis by Chemicals.- 2.3. Effects of Immunosuppression on Development of Spontaneous Tumors.- 3. Spontaneous Immunosuppression and Malignancy in Experimental Animals.- 3.1. Congenitally Athymic (Nude) Mice.- 3.2. Immunocompetence of Animals with a High Incidence of Tumors.- 3.3. Immunosuppressionby Oncogenic Viruses.- 3.4. Immunosuppression by Carcinogenic Chemicals.- 4. Immunosuppression and Malignancy in Human Beings.- 4.1. Immunodeficiency Diseases.- 4.2. Neoplasms in Recipientsof Organ Allografts.- 5. Conclusions.- 6. References.- Pathogenesis of Plasmacytomas in Mice.- 1. Introduction.- 2. "Spontaneous" Plasmacytomas.- 2.1. Ileocecal Plasmacytomas in Mice.- 2.2. Ileocecal Immunocytomas in Rats.- 2.3. Comment.- 3. Induced Plasmacytomas in Mice.- 3.1. Plasmacytomagenic Peritoneal Granuloma Inducing Agents.- 3.2. Genetic Basis of Susceptibility.- 3.3. The Peritoneal Site.- 3.4. Role of the Oil Granuloma.- 3.5. Role of Viruses in Plasmacytoma Development.- 4. Summary.- 5. References.- Chemical Carcinogenesis.- Metabolism of Chemical Carcinogens.- 1. Cancer, a Class of Diseases Due Mainly to Environmental Factors: Synthetic or Naturally Occurring.- 2. Types of Chemical Carcinogens.- 3. Metabolism of Chemical Carcinogens.- 3.1. Direct-Acting Carcinogens.- 3.2. Procarcinogens.- 3.3. Specific Activation and Metabolic Systems.- 4. Variation in Carcinogen Metabolism.- 4.1. Species and Strain.- 4.2. Sex and Endocrine Status.- 4.3. Age.- 5. Modification of Carcinogen Metabolism.- 5.1. Diet.- 5.2. Effect of Mode and Frequency of Exposure.- 5.3. Effect of Other Agents.- 5.4. Chemical Carcinogens and Mutagens.- 6. Concluding Remarks and Prospects.- 7. References.- Chemical Carcinogenesis: Interactions of Carcinogens with Nucleic Acids.- 1. Introduction.- 2. Interaction of Chemical Carcinogens with DNA.- 2.1. Covalent Interactions.- 2.2. Noncovalent Interactions.- 2.3. Purine-N-Oxides.- 2.4. Carcinogenic Metals.- 3. Interaction of Chemical Carcinogens with Mitochondrial DNA.- 4. Interaction of Chemical Carcinogens with RNA.- 4.1. General.- 4.2. Alkylating Agents.- 4.3. Aromatic Amines and Amides.- 4.4. Polycyclic Aromatic Hydrocarbons.- 4.5. 4-Nitroquinoline-N-Oxide.- 5. Influence of Carcinogen-Nucleic Acid Interactions on the Structure, Synthesis, and Function of DNA and RNA.- 5.1. Alterations in DNA Structure.- 5.2. Alterations in the Synthesis and Function of DNA and RNA.- 6. Carcinogen-DNA Interaction and Carcinogenesis.- 6.1. Carcinogen-DNA Interaction: Quantitative Analysis.- 6.2. Carcinogen-DNA Interaction: Qualitative Analysis.- 6.3. Repair in Vivo of DNA Damage Induced by Chemical Carcinogens.- 7. Perspectives and Conclusions.- 8. References.- Some Effects of Chemical Carcinogens on Cell Organelles.- 1. Introduction.- 2. The Carcinogens.- 2.1. Aflatoxins.- 2.2 Azo Dyes.- 2.3. Ethionine.- 2.4. Nitrosamines.- 2.5. Pyrrolizidine Alkaloids.- 2.6. Thioacetamide.- 3. Organelles.- 3.1. Endoplasmic Reticulum.- 3.2. Plasma Membrane.- 3.3. Mitochondria, Lysosomes, Microbodies.- 3.4. Nucleolus.- 4…