1 Introduction to Cell Growth: Growth in Size and DNA Replication.- A. Introduction.- B. Doubling of Size in Growing Cells.- C. Replication of DNA in Growing Cells.- D. Independence of Signal to Grow in Size from Signal to Replicate DNA.- E. Mechanism of Action of Growth Factors.- References.- 2 Survival and Growth Requirements of Nontransformed Cells..- A. Definitions.- I. Normal, Nontransformed, and Transformed Cells.- II. Survival and Survival Requirements.- III. Cell Cycle, Growth, Division, Multiplication, and Proliferation.- IV. Nutrient, Growth Requirement, Growth Factor, Mitogen, and Hormone.- B. Assay Systems for the Measurement of Growth Requirements.- I. Background.- II. Inadequacy for Nontransformed Cells of Classic Assay Systems.- 1. Evolutionary Adaptation of Permanent Lines.- 2. Role of Serum in the Multiplication of Nontransformed Cells.- 3. Problems Awaiting Solution for Nontransformed Cells.- III. Holistic Approach to Cellular Growth Requirements.- IV. Development of Specific Assays for Individual Growth Requirements.- 1. Background Media Lacking a Single Growth-Promoting Substance.- 2. First Limiting Factor.- 3. Replaceable Requirements.- 4. Sequential Depletion.- 5. Systematic Testing of Suspected Growth-Promoting Substances.- V. Types of Measurement and Analysis of Data.- 1. Short-Term Vs Long-Term Multiplication.- 2. Sparse Vs Dense Cultures.- 3. DNA Synthesis Vs Increase in Cell Number.- 4. Analysis of Data Based on Total Multiplication.- 5. Analysis Based on Rate of Multiplication.- 6. Multiplication Rate Kinetics.- VI. Systematic Analysis of Growth Requirements.- C. Requirements for Survival and Growth of Nontransformed Cells.- I. Transformed Vs Nontransformed Cells.- II. Requirements Related to Subculturing and Cellular Attachment.- 1. Anchorage Dependence.- 2. Neutralization of the Dispersing Agent.- 3. Low Temperature Trypsinization.- 4. Attachment and Spreading Factors.- 5. The Culture Surface.- 6. Artificial Substitutes for the Basement Membrane.- III. Inorganic Ions, Physical Chemistry, and Cell Physiology.- 1. Bicarbonate, Carbon Dioxide, pH, and Buffering.- 2. Sodium, Chloride, Osmolarity, and Humidification of Incubators.- 3. Potassium and Na+: K+ Ratios.- 4. Calcium, Magnesium, and Regulatory Roles of Divalent Cations.- 5. Phosphate.- 6. Other Physicochemical Parameters.- IV. Qualitative Nutrient Requirements.- 1. Components of Eagle’s Minimum Essential Medium.- 2. Other Amino Acids.- 3. Other Vitamins.- 4. Carbohydrates and Intermediates of Energy Metabolism.- 5. Nucleic Acid Components.- 6. Other Organic Nutrients.- 7. Inorganic Trace Elements.- V. Quantitative Optimization of Synthetic Media.- 1. Species and Cell Type Individuality of Quantitative Requirements.- 2. Reduction of Requirements for Serum and Growth Factors.- VI. Lipids and Related Substances.- 1. Fatty Acids.- 2. Prostaglandins.- 3. Phospholipids.- 4. Cholesterol.- 5. Synthetic Media.- VII. Hormones, Hormone-Like Growth Factors, and Carrier Proteins.- 1. Hormones.- 2. Growth Factors.- 3. Replacement of Serum with Hormones and Growth Factors.- 4. Individuality of Cellular Requirements.- 5. Nontransformed Cells.- 6. Relationship to In Vivo Growth Requirements.- VIII. Special Requirements Related to Cellular Density.- 1. Requirements for Clonal Growth.- 2. Requirements for Multiplication of Dense Cultures.- IX. Regulatory Interactions and Artificial Stimulation of Multiplication.- 1. Borderline Toxicity.- 2. Proteolytic Enzymes.- 3. Tumor Promoters.- 4. Inorganic Ions.- 5. Cyclic Nucleotides.- 6. Defining a Genuine Growth Requirement.- D. Requirements for Survival of Nontransformed Cells Without Proliferation.- I. Early Studies.- II. Survival Factor.- III. Elimination of the Need for Survival Factor.- IV. Nutrients and Survival.- V. Differences in Survival Between Nontransformed and Transformed Cells.- E. Future Studies of the Growth and Survival Requirements of Nontransformed Cells.- I. Integration of New Findings.- II. Questions Remaining to be Solved After Development Synthetic Media.- III. Magnitude of Remaining Work.- IV. Selective Allocation of Resources.- F. Summary and Conclusions.- G. Note Added in Proof.- References.- 3 Epidermal Growth Factor.- A. Introduction.- B. Chemical and Physical properties of EGF.- I. Mouse EGF.- 1. Isolation.- 2. Chemical and Physical Properties.- 3. Derivatives.- a) EGF-2.- b) EGF-5.- c) Cyanogen Bromide EGF.- 4. High Molecular Weight Mouse EGF.- II. Human EGF.- 1. Identification and Isolation.- 2. Chemical and Physical Properties.- 3. Relationship of Human EGF and Urogastrone.- III. Rat EGF.- C. Physiological Aspects of EGF.- I. Concentration in Body Fluids.- 1. Mouse EGF.- 2. Human EGF.- II. Localization.- 1. Mouse EGF.- 2. Human EGF.- III. Control of Submaxillary Gland Content of Mouse EGF.- IV. Secretion of Mouse EGF from the Submaxillary Gland.- V. Factors Affecting Levels of Human EGF.- D. Biological Activities of EGF In Vivo.- I. Skin.- II. Corneal Epithelium.- III. Respiratory Epithelium.- IV. Gastrointestinal Tract.- V. Liver.- E. Organ Culture Studies of EGF.- I. Skin.- II. Other Tissues.- 1. Cornea.- 2. Palate.- 3. Bone.- F. Cell Culture Studies of EGF.- I. Cell Nutrition.- II. Types of Cells Affected by EGF.- III. EGF and the Growth of Cell Populations.- IV. Components of the Mitogenic Response.- 1. Rapid Biological Responses at the Membrane.- a) Uridine Uptake.- b) Sugar Transport.- c) Cation Fluxes.- d) Putrescine Transport.- e) Alanine Transport.- f) Membrane Ruffling and Macropinocytosis.- g) Other Membrane Responses.- 2. Responses of EGF Occurring in the Cytoplasm.- a) Activation of Glycolysis.- b) Synthesis of Extracellular Macromolecules.- c) Activation of RNA and Protein Synthesis.- d) Activation of Ornithine Decarboxylase.- e) Protein Phosphorylation.- 3. Stimulation of DNA Synthesis.- V. Responses Not Related to Mitogenesis.- G. Growth Factor: Receptor Interactions.- I. Receptors for EGF.- II. Internalization and Degradation of EGF.- 1. Biochemical Evidence.- 2. Morphological Evidence.- III. Internalization of the Receptor.- 1. Indirect Evidence.- 2. Chemical Evidence.- 3. Morphological Evidence.- IV. Recovery of Receptor Activity.- H. Relationship of EGF Binding and Metabolism to Biological Activity.- I. Rapid Changes in Cell Physiology.- II. Stimulation of DNA Synthesis.- I. Other Controls of Receptor Activity.- I. Transforming Agents.- II. Tumor Promoters.- III. Differentiation.- IV. Lectins and Glycoprotein Metabolism.- V. Glucocorticoids.- VI. Modulation of Protein Synthesis.- K. A Biochemical Response to EGF in Subcellular Systems.- L. Prospectus.- References.- 4 The Platelet-Derived Growth Factor.- A. Serum, the Platelet-Derived Growth Factor, and Cell Culture.- B. The Platelet.- C. Platelet-Structure and function.- D. The Gray Platelet Syndrome.- E. The Megakaryocyte as the Source of Platelet-Derived Growth Factor.- F. Purification and Characterization of the Platelet-Derived Growth Factor.- G. The Spectrum of Cell Response.- H. Control of Cell Proliferation by Platelet-Derived Growth Factor and Plasma.- I. The Role of Plasma.- K. Endocytosis and the Platelet-Derived Growth Factor.- L. Modulation of Receptors for Epidermal Growth Factor by Platelet-Derived Growth Factor.- M. Lipid Metabolism and the Platelet-Derived Growth Factor.- N. Platelets and Cell Proliferation In Vivo.- O. Summary.- References.- 5 Somatomedin: Physiological Control and Effects on Cell Proliferation.- A. Introduction.- B. Assay Systems Used to Measure Somatomedins.- I. Biological Assays.- II. Radioreceptor Assays.- III. Protein Binding Assays.- IV. Radioimmunoassays.- V. Standards Used for the Quantitation of Somatomedin Activity.- C. Isolation and Properties of the Individual Somatomedins.- I. Basic Somatomedins.- 1. Somatomedin-C (SM-C).- 2. Insulin-Like Growth Factor I (IGF-I).- 3. Somatomedin in Other Species.- II. Neutral Somatomedins.- 1. Insulin-Like Growth Factor II (IGF-II).- 2. Somatomedin-A (SM-A).- 3