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Extrapolation of Radiation-induced Cancer Risks from Nonhuman Experimental Systems to Humans
(N C R P Report Nro. 150)
By
National Council on Radiation Protection
Publisher
National Council of Teachers of English
Number Of Pages: 267
Publication Date: 2005-11
ISBN-10 / ASIN: 092960086X
ISBN-13 / EAN: 9780929600864
Description
:gift::gift:
Extrapolation of Radiation-induced Cancer Risks from Nonhuman Experimental Systems to Humans
(N C R P Report Nro. 150)
By
National Council on Radiation Protection
Publisher
National Council of Teachers of English
Number Of Pages: 267
Publication Date: 2005-11
ISBN-10 / ASIN: 092960086X
ISBN-13 / EAN: 9780929600864
Description
This Report reviews the scientific issues associated with the extrapolation of radiation-induced cancer risks from nonhuman experimental systems to humans. The basic principles of radiation effects at the molecular and cellular level are examined with emphasis on comparisons among various species including humans. These comparisons among species are then continued for cancers of similar cell types in the same organ system. Risk estimates are made from an observed level of effect as a function of organ dose. The major organ systems are individually considered. Extrapolation models are reviewed and include external and internal radiation exposures.
Table of Contents
Preface
1. Executive Summary and Recommendations
1.1 Why Is Extrapolation Still Required?
1.2 Summary of Findings
1.2.1 Historical Aspects
1.2.2 Neoplastic Disease
1.2.2.1 Hematopoietic System
1.2.2.2 Lung
1.2.2.3 Breast
1.2.2.4 Thyroid
1.2.2.5 Skin
1.2.2.6 Gastrointestinal Track
1.2.2.7 Bone
1.2.3 Somatic Genetic Damage at Molecular and Cellular Levels
1.2.4 Extrapolation Models and Methods
1.2.4.1 Toxicity of Chemotherapeutic Drugs
1.2.4.2 Life Shortening
1.2.4.3 Interspecies Prediction of Life Shortening and Cancer from External Irradiation
1.2.4.4 Extrapolation of Dose-Rate Effectiveness Factors
1.2.4.5 Interspecies Prediction of Injury from Internally-Deposited Radionuclides
1.3 Conclusions
1.4 Recommendations
2. Introduction
3. History of Extrapolation: Nonhuman Experimental Systems to Humans
3.1 Introduction
3.2 Lessons Learned from Genetic Risks
3.2.1 Methods of Estimation
3.2.1.1 Doubling-Dose Method
3.2.1.2 Direct Method
3.2.1.3 Gene-Number Method
3.2.2 Discussion of Methods of Estimating Genetic Risk
3.2.3 Role of Genetics in the Estimation of Somatic Risks
3.3 Somatic Risks
4. Tissue and Organ Differences Among Species with Emphasis on the Cells of Origin of Cancers
4.1 Introduction
4.2 Hematopoietic System
4.2.1 Introduction: Leukemias and Lymphomas
4.2.2 Comparison of Radiation-Induced Leukemias Among Species
4.2.3 Pathology and Dose-Response Relationships
4.2.4 Comparison of Hematopoietic Systems
4.2.5 Target Cells
4.2.6 Comparison of Cytogenetic Processes: Common or Species-Specific Patterns
4.2.7 Leukemogenesis Resulting from Gene Rearrangements
4.2.8 Secondary Cytogenetic Lesions Associated with Leukemia Promotion and Progression
4.2.9 Hematopoietic Cell Origins of the Putative “Critical” Genic Lesions and the Nature of Induced Genic Dysfunctions
4.2.10 Cooperating Oncogenes in Lymphoid Neoplasias
4.2.11 Cooperating Oncogenes in Myeloid Neoplasias
4.2.12 Hematopoeitic Microenvironment
4.2.13 Summary
4.3 Lung
4.3.1 Introduction
4.3.2 Adenocarcinoma
4.3.3 Squamous-Cell Carcinoma
4.3.4 Small-Cell Lung Carcinoma
4.3.5 Large-Cell Carcinoma
4.3.6 Summary
4.4 Breast
4.4.1 Histogenesis of Mammary Glands and MammaryCancer
4.4.2 Hormones and Mammary Carcinogenesis
4.4.3 Cellular Origins of Mammary Cancer
4.4.4 Summary
4.5 Thyroid
4.5.1 General Background
4.5.2 Histogenesis of the Thyroid Gland and Thyroid Cancer
4.5.3 Thyroid Function and its Control
4.5.4 Cellular Economy of the Thyroid Gland and the Origin of Cancer
4.5.5 Summary
4.6 Skin
4.6.1 Introduction
4.6.2 Epidermal Cancers
4.6.3 Melanoma
4.6.4 Tumors of the Dermis
4.6.5 Mechanisms of Epidermal Carcinogenesis
4.6.6 Importance of Interactions
4.6.7 Summary
4.7 Gastrointestinal Tract
4.7.1 Introduction
4.7.2 Stomach
4.7.3 Small Intestine
4.7.4 Colorectal Tumors
4.7.5 Summary
4.8 Bone
4.8.1 Humans
4.8.2 Mice
4.8.3 Rats
4.8.4 Dogs
4.8.5 Summary
5. Radiation Effects at the Molecular and Cellular Levels
5.1 Introduction
5.2 Effects of Ionizing Radiations at the Molecular Level. . 85
5.2.1 DNA Damage
5.2.2 Repair of DNA Damage
5.2.2.1 Single-Strand Breaks
5.2.2.2 Double-Strand Breaks
5.2.2.2.1 Nonhomologous End-Joining
5.2.2.2.2 Recombination Repair
5.2.2.3 Base Damage Repair
5.2.3 Characterization of Genes (Enzymes) Involved in DNA Repair
5.2.4 DNA Repair and Cell-Cycle Progression
5.2.5 Genetic Susceptibility to Ionizing Radiations
5.2.6 Conclusions
5.3 Effects of Ionizing Radiations at the Cellular Level
5.3.1 Point (or Gene) Mutations
5.3.2 Chromosome Aberrations and Deletion Mutations
5.3.3 Use of Mechanistic Data on Mutation and Chromosome Aberration Induction
5.3.4 Cell Killing
5.3.5 Potential Confounders of Dose-Response Curves
5.3.5.1 Bystander Effects
5.3.5.2 Genomic Instability
5.3.5.3 Adaptive Responses
5.3.6 Genetic Alterations in Tumors in Humans and Rodents
5.3.6.1 Oncogene Activation
5.3.6.2 Tumor-Suppressor Genes
5.3.7 Conclusions
6. Extrapolation Models
6.1 Interspecies Correlations of Chemical Toxicities
6.1.1 Introduction
6.1.2 Acute Toxicity
6.1.3 Chronic Toxicity
6.2 Interspecies Prediction of Summary Measures of Mortality: Relative Risk Models
6.3 Interspecies Correlations of Radiation Effects
6.3.1 Introduction
6.3.2 Predictions of Radiation-Induced Mortality
6.3.3 Example of Interspecies Prediction for Single Exposure
6.3.4 Conclusion
6.4 Interspecies Prediction of Age-Specific Mortality
6.4.1 Introduction
6.4.2 Background and Justification for Interspecies Predictions
6.4.3 Continuous Exposure: Mice to Dogs
6.4.4 Single Exposure: Mice to Dogs and Humans
6.4.5 Conclusion
6.5 Extrapolation of Dose-Rate Effectiveness Factors
6.5.1 Requirements and Limitations
6.5.2 Conclusion
6.6 Extrapolation of Results for Internally-Deposited Radionuclides from Laboratory Animals to Humans
6.6.1 Temporal Pattern of Delivery of Radiation Dose
6.6.2 Spatial Pattern of Delivery of Dose
6.6.3 Linear-Energy Transfer (Radiation Quality)
6.6.4 Internally-Deposited Radionuclides for Which Human and Laboratory Animal Data are Available
6.6.4.1 Radium-226, 228
6.6.4.2 Radium-224
6.6.4.3 Thorotrast® (232Th)
6.6.4.4 Radon and Radon Progeny
6.6.5 Examples of Internally-Deposited Radionuclides for Which Laboratory Animal Data are Available and for Which Links Could be Made to Human Data
6.6.5.1 Bone Cancer
6.6.5.2 Liver Cancer
6.6.5.3 Lung Cancer
6.6.6 Examples of Linking Risks from Laboratory Animals to Human Data
6.6.6.1 Bone Cancer
6.6.6.2 Lung Cancer
7. Summary
7.1 Introduction
7.2 Summary
7.2.1 History of Extrapolation from Nonhuman Experimental Systems to Humans
7.2.2 Cells of Origin of Cancer in Different Animal Species
7.2.3 Radiation Effects at the Molecular and Cellular Levels
7.2.4 Extrapolation Models
Glossary
Symbols and Acronyms
References
The NCRP
NCRP Publications
Index
Table of Contents
Preface
1. Executive Summary and Recommendations
1.1 Why Is Extrapolation Still Required?
1.2 Summary of Findings
1.2.1 Historical Aspects
1.2.2 Neoplastic Disease
1.2.2.1 Hematopoietic System
1.2.2.2 Lung
1.2.2.3 Breast
1.2.2.4 Thyroid
1.2.2.5 Skin
1.2.2.6 Gastrointestinal Track
1.2.2.7 Bone
1.2.3 Somatic Genetic Damage at Molecular and Cellular Levels
1.2.4 Extrapolation Models and Methods
1.2.4.1 Toxicity of Chemotherapeutic Drugs
1.2.4.2 Life Shortening
1.2.4.3 Interspecies Prediction of Life Shortening and Cancer from External Irradiation
1.2.4.4 Extrapolation of Dose-Rate Effectiveness Factors
1.2.4.5 Interspecies Prediction of Injury from Internally-Deposited Radionuclides
1.3 Conclusions
1.4 Recommendations
2. Introduction
3. History of Extrapolation: Nonhuman Experimental Systems to Humans
3.1 Introduction
3.2 Lessons Learned from Genetic Risks
3.2.1 Methods of Estimation
3.2.1.1 Doubling-Dose Method
3.2.1.2 Direct Method
3.2.1.3 Gene-Number Method
3.2.2 Discussion of Methods of Estimating Genetic Risk
3.2.3 Role of Genetics in the Estimation of Somatic Risks
3.3 Somatic Risks
4. Tissue and Organ Differences Among Species with Emphasis on the Cells of Origin of Cancers
4.1 Introduction
4.2 Hematopoietic System
4.2.1 Introduction: Leukemias and Lymphomas
4.2.2 Comparison of Radiation-Induced Leukemias Among Species
4.2.3 Pathology and Dose-Response Relationships
4.2.4 Comparison of Hematopoietic Systems
4.2.5 Target Cells
4.2.6 Comparison of Cytogenetic Processes: Common or Species-Specific Patterns
4.2.7 Leukemogenesis Resulting from Gene Rearrangements
4.2.8 Secondary Cytogenetic Lesions Associated with Leukemia Promotion and Progression
4.2.9 Hematopoietic Cell Origins of the Putative “Critical” Genic Lesions and the Nature of Induced Genic Dysfunctions
4.2.10 Cooperating Oncogenes in Lymphoid Neoplasias
4.2.11 Cooperating Oncogenes in Myeloid Neoplasias
4.2.12 Hematopoeitic Microenvironment
4.2.13 Summary
4.3 Lung
4.3.1 Introduction
4.3.2 Adenocarcinoma
4.3.3 Squamous-Cell Carcinoma
4.3.4 Small-Cell Lung Carcinoma
4.3.5 Large-Cell Carcinoma
4.3.6 Summary
4.4 Breast
4.4.1 Histogenesis of Mammary Glands and MammaryCancer
4.4.2 Hormones and Mammary Carcinogenesis
4.4.3 Cellular Origins of Mammary Cancer
4.4.4 Summary
4.5 Thyroid
4.5.1 General Background
4.5.2 Histogenesis of the Thyroid Gland and Thyroid Cancer
4.5.3 Thyroid Function and its Control
4.5.4 Cellular Economy of the Thyroid Gland and the Origin of Cancer
4.5.5 Summary
4.6 Skin
4.6.1 Introduction
4.6.2 Epidermal Cancers
4.6.3 Melanoma
4.6.4 Tumors of the Dermis
4.6.5 Mechanisms of Epidermal Carcinogenesis
4.6.6 Importance of Interactions
4.6.7 Summary
4.7 Gastrointestinal Tract
4.7.1 Introduction
4.7.2 Stomach
4.7.3 Small Intestine
4.7.4 Colorectal Tumors
4.7.5 Summary
4.8 Bone
4.8.1 Humans
4.8.2 Mice
4.8.3 Rats
4.8.4 Dogs
4.8.5 Summary
5. Radiation Effects at the Molecular and Cellular Levels
5.1 Introduction
5.2 Effects of Ionizing Radiations at the Molecular Level. . 85
5.2.1 DNA Damage
5.2.2 Repair of DNA Damage
5.2.2.1 Single-Strand Breaks
5.2.2.2 Double-Strand Breaks
5.2.2.2.1 Nonhomologous End-Joining
5.2.2.2.2 Recombination Repair
5.2.2.3 Base Damage Repair
5.2.3 Characterization of Genes (Enzymes) Involved in DNA Repair
5.2.4 DNA Repair and Cell-Cycle Progression
5.2.5 Genetic Susceptibility to Ionizing Radiations
5.2.6 Conclusions
5.3 Effects of Ionizing Radiations at the Cellular Level
5.3.1 Point (or Gene) Mutations
5.3.2 Chromosome Aberrations and Deletion Mutations
5.3.3 Use of Mechanistic Data on Mutation and Chromosome Aberration Induction
5.3.4 Cell Killing
5.3.5 Potential Confounders of Dose-Response Curves
5.3.5.1 Bystander Effects
5.3.5.2 Genomic Instability
5.3.5.3 Adaptive Responses
5.3.6 Genetic Alterations in Tumors in Humans and Rodents
5.3.6.1 Oncogene Activation
5.3.6.2 Tumor-Suppressor Genes
5.3.7 Conclusions
6. Extrapolation Models
6.1 Interspecies Correlations of Chemical Toxicities
6.1.1 Introduction
6.1.2 Acute Toxicity
6.1.3 Chronic Toxicity
6.2 Interspecies Prediction of Summary Measures of Mortality: Relative Risk Models
6.3 Interspecies Correlations of Radiation Effects
6.3.1 Introduction
6.3.2 Predictions of Radiation-Induced Mortality
6.3.3 Example of Interspecies Prediction for Single Exposure
6.3.4 Conclusion
6.4 Interspecies Prediction of Age-Specific Mortality
6.4.1 Introduction
6.4.2 Background and Justification for Interspecies Predictions
6.4.3 Continuous Exposure: Mice to Dogs
6.4.4 Single Exposure: Mice to Dogs and Humans
6.4.5 Conclusion
6.5 Extrapolation of Dose-Rate Effectiveness Factors
6.5.1 Requirements and Limitations
6.5.2 Conclusion
6.6 Extrapolation of Results for Internally-Deposited Radionuclides from Laboratory Animals to Humans
6.6.1 Temporal Pattern of Delivery of Radiation Dose
6.6.2 Spatial Pattern of Delivery of Dose
6.6.3 Linear-Energy Transfer (Radiation Quality)
6.6.4 Internally-Deposited Radionuclides for Which Human and Laboratory Animal Data are Available
6.6.4.1 Radium-226, 228
6.6.4.2 Radium-224
6.6.4.3 Thorotrast® (232Th)
6.6.4.4 Radon and Radon Progeny
6.6.5 Examples of Internally-Deposited Radionuclides for Which Laboratory Animal Data are Available and for Which Links Could be Made to Human Data
6.6.5.1 Bone Cancer
6.6.5.2 Liver Cancer
6.6.5.3 Lung Cancer
6.6.6 Examples of Linking Risks from Laboratory Animals to Human Data
6.6.6.1 Bone Cancer
6.6.6.2 Lung Cancer
7. Summary
7.1 Introduction
7.2 Summary
7.2.1 History of Extrapolation from Nonhuman Experimental Systems to Humans
7.2.2 Cells of Origin of Cancer in Different Animal Species
7.2.3 Radiation Effects at the Molecular and Cellular Levels
7.2.4 Extrapolation Models
Glossary
Symbols and Acronyms
References
The NCRP
NCRP Publications
Index
