Experimental Leukemia and Mammary Cancer
Induction, Prevention, Cure
9780226358604
Experimental Leukemia and Mammary Cancer
Induction, Prevention, Cure
Charles Brenton Huggins won the Nobel prize in 1966 for his extensive work in cancer research. He has spent fifty years at the laboratory bench exploring the nature of this disease in an attempt to understand and control it. In this volume, based almost exclusively on experiments conducted over the past twenty years at the University of Chicago, is both the record of Huggins’s own research and, in Huggins’s words, "a do-it-yourself guide for cancer research workers." Written simply and clearly so that the experiments can be easily reproduced, the book presents Huggins’s experiments in the induction of breast cancer and leukemia in rodents. It also describes the methods he discovered to prevent cancer and to cure many of the cancers he has been able to induce. Although most of the material concerns breast cancer and leukemia, research on other kinds of tumors is also described.
Table of Contents
Preface
Acknowledgments
Abbreviations and Trivial Names
1. The Cancer Cell
Specific Changes in Chromosomes: The Karyotype
Detection of Chemical Mutagens
Glycolysis
Enzyme Patterns
Cell Surface Effects
Lectins
2. Changing the Cell’s Phenotype with Epithelium, Virus, or Solid States
Transforming Epithelium: Normal Fibroblast to Normal Osteoblast
Rous Sarcoma Virus-I: Transformation of Normal Fibroblasts into Malignant Ones
Rous Sarcoma Virus-II: Transformation of Normal Fibroblasts into Malignant Osteoblasts
Avian Leukemia Viruses
DNA-Containing Tumor Viruses: The Shope Papilloma Virus
DNA-Containing Tumor Viruses: Polyoma and Marek Disease
RNA-Containing Tumor Viruses: Erythroleukemia and Lymphocytic Leukemia
RNA-Containing Mammary Tumor Virus
Replication of RNA-Containing Tumor Viruses
Virus Transformation of Fibroblasts in Tissue Culture
Solid-State Carcinogenesis with Plastics: Transformation of Fibroblasts into Sarcoma
3. Hormones and Cancer
Five Estrogens
Structure-Function Relations of Estrogens and Androgens
Estrogen Antagonists
Mechanisms of Hormone Action: Cyclic AMP
Mechanisms of Hormone Action: Estrogen Receptors
Hormone-Induced Growth of Mammary Gland
Hyperplastic Alveolar Nodules
Endocrine Induction of Experimental Cancer
Endocrine Prevention of Cancer
Endocrine-Induced Remission of Cancer
Obligatory Growth
Mammary Cancer in Dog and Adrenal Cortical Tumors
4. The Road to 7,12-DMBA and 7,8,12-TMBA
Human Cancer Caused by Soot
Experimental Cancer Produced by Coal Tar
Carcinogenic Tars Produced in the Laboratory
Isolation of Pure Carcinogenic Hydrocarbons
Metabolism of 7,12-DMBA
Aromatic Amines: Anesthetic Carcinogens
5. Induction of Sarcoma
Radiation-Induced Fibrosarcoma
Sarcoma Induced Locally by Hydrocarbons
Sarcoma Induced Remotely by 3-MC
Intraperitoneal Administration of 7,12-DMBA
6. Induction of Mammary Cancer in Rat
Radiation-Induced Mammary Carcinoma
Hydrocarbon-Induced Mammary Carcinoma
Carcinogenic Emulsions for Intravenous Injection
Mammary Cancer in Ovariex Rat
Mammary Cancer in Hypox Rat
Molecular Characteristics of Mammary Carcinogens
Biological Characteristics of Mammary Carcinoma
Enzymes in Mammary Carcinoma
Estrogen Receptors in Experimental Mammary Cancer
Genetic Constitution, Mammary Cancer, and Endocrine Status of Rat Strains
Growth Rate and Sexual Maturity
7. Acceleration and Extinction of Mammary Cancer
Hypophysectomy and Ovariectomy
Estradiol, Progesterone, and Gonadotrophin
Polyestradiol Phosphate
Anti-Estrogens in the Treatment of Mammary Cancer
Pregnancy and Lactation
Hypothalamus and Prolactin
Prolactin Receptors
8. Induction and Extinction of Leukemia in Rat
Induction of Leukemia
Leukemia in S-D Rat
Leukemia in L-E Rat
Recognition of Leukemia
Transplantation of Blood from Leukemic Donors
Types of Hydrocarbon-Induced Leukemia
Extinction of Leukemia by Endocrine Methods
Erythroleukemia, Anemia, and Erythropoietin
9. Selective Cell Destruction in the Adrenal Cortex and Testis Produced by 7,12-DMBA
Adrenal Apoplexy
Hydrocarbon-Induced Adrenal Destruction
Corticotrophin-Dependence of Adrenal Apoplexy
Molecular Structure of Corticolytic Hydrocarbons
Prevention of Adrenal Damage by Enzyme Inhibitors
Selective Destruction in Testis
10. Prevention of Hydrocarbon-Induced Leukemia and Mammary Cancer
Prevention of Azo Dye-Induced Liver Tumors
Drug-Metabolizing Enzymes
Prevention of 7,12-DMBA-Produced Adrenal Apoplexy
Microsome-Bound Drug-Metabolizing Enzymes
Azo Dye-Induced Prevention of Mammary Cancer
Azo Dye-Induced Prevention of Hydrocarbon-Induced Leukemia
Failure of Sudan III To Elicit Tumors
Preservation of Life of Rats Given a Massive Dose of 7,12-DMBA
11. Lymphomas and Ovarian Tumors Elicited by 7,12-DMBA in Mouse
Hydrocarbon-Induced Neoplasms in Inbred Mice
Hydrocarbon-Induced Neoplasms in Noninbred Mice
Toxicity of 7,12-DMBA and 7,8,12-TMBA
Induction of Leukemia by Intravenous Injection of 7,12-DMBA in Mouse
Induction of Leukemia by Feeding 7,12-DMBA in Mouse
Inoculation of Newborn Mice with Leukemic Blood
Influence of Adrenalectomy and Glucocorticoids on Lymphomas
L-asparaginase-Induced Regression of Lymphomas
Glucocorticoid-Induced Regression of Transplanted Leukemia and Lymphosarcoma
Immunologic Inhibition of the Adenohypophysis
Appendix 1: Endocrine-Induced Regression of Cancers
Appendix 2: Composition and Preparation of Experimental Intravenous Fat Emulsions, by Paul E. Schurr
References
Index
Acknowledgments
Abbreviations and Trivial Names
1. The Cancer Cell
Specific Changes in Chromosomes: The Karyotype
Detection of Chemical Mutagens
Glycolysis
Enzyme Patterns
Cell Surface Effects
Lectins
2. Changing the Cell’s Phenotype with Epithelium, Virus, or Solid States
Transforming Epithelium: Normal Fibroblast to Normal Osteoblast
Rous Sarcoma Virus-I: Transformation of Normal Fibroblasts into Malignant Ones
Rous Sarcoma Virus-II: Transformation of Normal Fibroblasts into Malignant Osteoblasts
Avian Leukemia Viruses
DNA-Containing Tumor Viruses: The Shope Papilloma Virus
DNA-Containing Tumor Viruses: Polyoma and Marek Disease
RNA-Containing Tumor Viruses: Erythroleukemia and Lymphocytic Leukemia
RNA-Containing Mammary Tumor Virus
Replication of RNA-Containing Tumor Viruses
Virus Transformation of Fibroblasts in Tissue Culture
Solid-State Carcinogenesis with Plastics: Transformation of Fibroblasts into Sarcoma
3. Hormones and Cancer
Five Estrogens
Structure-Function Relations of Estrogens and Androgens
Estrogen Antagonists
Mechanisms of Hormone Action: Cyclic AMP
Mechanisms of Hormone Action: Estrogen Receptors
Hormone-Induced Growth of Mammary Gland
Hyperplastic Alveolar Nodules
Endocrine Induction of Experimental Cancer
Endocrine Prevention of Cancer
Endocrine-Induced Remission of Cancer
Obligatory Growth
Mammary Cancer in Dog and Adrenal Cortical Tumors
4. The Road to 7,12-DMBA and 7,8,12-TMBA
Human Cancer Caused by Soot
Experimental Cancer Produced by Coal Tar
Carcinogenic Tars Produced in the Laboratory
Isolation of Pure Carcinogenic Hydrocarbons
Metabolism of 7,12-DMBA
Aromatic Amines: Anesthetic Carcinogens
5. Induction of Sarcoma
Radiation-Induced Fibrosarcoma
Sarcoma Induced Locally by Hydrocarbons
Sarcoma Induced Remotely by 3-MC
Intraperitoneal Administration of 7,12-DMBA
6. Induction of Mammary Cancer in Rat
Radiation-Induced Mammary Carcinoma
Hydrocarbon-Induced Mammary Carcinoma
Carcinogenic Emulsions for Intravenous Injection
Mammary Cancer in Ovariex Rat
Mammary Cancer in Hypox Rat
Molecular Characteristics of Mammary Carcinogens
Biological Characteristics of Mammary Carcinoma
Enzymes in Mammary Carcinoma
Estrogen Receptors in Experimental Mammary Cancer
Genetic Constitution, Mammary Cancer, and Endocrine Status of Rat Strains
Growth Rate and Sexual Maturity
7. Acceleration and Extinction of Mammary Cancer
Hypophysectomy and Ovariectomy
Estradiol, Progesterone, and Gonadotrophin
Polyestradiol Phosphate
Anti-Estrogens in the Treatment of Mammary Cancer
Pregnancy and Lactation
Hypothalamus and Prolactin
Prolactin Receptors
8. Induction and Extinction of Leukemia in Rat
Induction of Leukemia
Leukemia in S-D Rat
Leukemia in L-E Rat
Recognition of Leukemia
Transplantation of Blood from Leukemic Donors
Types of Hydrocarbon-Induced Leukemia
Extinction of Leukemia by Endocrine Methods
Erythroleukemia, Anemia, and Erythropoietin
9. Selective Cell Destruction in the Adrenal Cortex and Testis Produced by 7,12-DMBA
Adrenal Apoplexy
Hydrocarbon-Induced Adrenal Destruction
Corticotrophin-Dependence of Adrenal Apoplexy
Molecular Structure of Corticolytic Hydrocarbons
Prevention of Adrenal Damage by Enzyme Inhibitors
Selective Destruction in Testis
10. Prevention of Hydrocarbon-Induced Leukemia and Mammary Cancer
Prevention of Azo Dye-Induced Liver Tumors
Drug-Metabolizing Enzymes
Prevention of 7,12-DMBA-Produced Adrenal Apoplexy
Microsome-Bound Drug-Metabolizing Enzymes
Azo Dye-Induced Prevention of Mammary Cancer
Azo Dye-Induced Prevention of Hydrocarbon-Induced Leukemia
Failure of Sudan III To Elicit Tumors
Preservation of Life of Rats Given a Massive Dose of 7,12-DMBA
11. Lymphomas and Ovarian Tumors Elicited by 7,12-DMBA in Mouse
Hydrocarbon-Induced Neoplasms in Inbred Mice
Hydrocarbon-Induced Neoplasms in Noninbred Mice
Toxicity of 7,12-DMBA and 7,8,12-TMBA
Induction of Leukemia by Intravenous Injection of 7,12-DMBA in Mouse
Induction of Leukemia by Feeding 7,12-DMBA in Mouse
Inoculation of Newborn Mice with Leukemic Blood
Influence of Adrenalectomy and Glucocorticoids on Lymphomas
L-asparaginase-Induced Regression of Lymphomas
Glucocorticoid-Induced Regression of Transplanted Leukemia and Lymphosarcoma
Immunologic Inhibition of the Adenohypophysis
Appendix 1: Endocrine-Induced Regression of Cancers
Appendix 2: Composition and Preparation of Experimental Intravenous Fat Emulsions, by Paul E. Schurr
References
Index