Translational Toxicology and Therapeutics

Description:

Written by leading research scientists, this book integrates current knowledge of toxicology and human health through coverage of environmental toxicants, genetic / epigenetic mechanisms, and carcinogenicity.

Provides information on lifestyle choices that can reduce cancer risk

Offers a systematic approach to identify mutagenic, developmental and reproductive toxicants

Helps readers develop new animal models and tests to assess toxic impacts of mutation and cancer on human health

Explains specific cellular and molecular targets of known toxicants operating through genetic and epigenetic mechanisms

Table of contents:

Part One: Introduction: The Case for Concern about Mutation and Cancer Susceptibility during Critical Windows of Development and the Opportunity to Translate Toxicology into a Therapeutic Discipline

Chapter 1: What Stressors Cause Cancer and When?

1.1 Introduction

1.2 What Stressors Cause Cancer and When?

1.3 Relevance of Circulating Cancer Markers

1.4 Potential Cancer Translational Toxicology Therapies

1.5 Modeling and the Future

References

Chapter 2: What Mutagenic Events Contribute to Human Cancer and Genetic Disease?

2.1 Introduction

2.2 Genetic Damage from Environmental Agents

2.3 Testing for Mutagenicity and Carcinogenicity

2.4 Predictive Toxicogenomics for Carcinogenicity

2.5 Germ Line Mutagenicity and Screening Tests

2.6 Reproductive Toxicology Assays in the Assessment of Heritable Effects

2.7 Assays in Need of Further Development or Validation

2.8 New Technologies

2.9 Endpoints Most Relevant to Human Genetic Risk

2.10 Worldwide Regulatory Requirements for Germ Cell Testing

2.11 Conclusion

Acknowledgments

References

Chapter 3: Developmental Origins of Cancer

3.1 Introduction

3.2 Current Trends in Childhood Cancer

3.3 Potential Mechanisms of Prenatal Cancer Induction

3.4 Ontogeny of Xenobiotic Metabolizing Enzymes and DNA Repair Systems

3.5 The Developmental Origins of Health and Disease (DOHaD) Theory

3.6 Epigenetic Regulation during Development

3.7 Mechanisms of Cancer in Offspring from Paternal Exposures

3.8 Parental Exposures Associated with Cancer in Offspring

3.9 Models for the Developmental Origins of Selected Cancers

3.10 Public Health Agencies' Views on Prenatal Exposures and Cancer Risk

3.11 Conclusions

Acknowledgment

References

Chapter 4: The Mechanistic Basis of Cancer Prevention

4.1 Introduction

4.2 A Mechanistic Approach

4.3 Preventing Cancer Attributable to Known Carcinogens

4.4 Prevention Involving Complex Risk Factors

4.5 Prevention Independent of Causative Agents or Risk Factors

4.6 Conclusion

References

Part Two: Exposures that Could Alter the Risk of Cancer Occurrence, and Impact Its Indolent or Aggressive Behavior and Progression Over Time

Chapter 5: Diet Factors in Cancer Risk

5.1 Introduction

5.2 Obesity

5.3 Macronutrients

5.4 Micronutrients

5.5 Phytochemicals

5.6 Conclusions

References

Chapter 6: Voluntary Exposures: Natural Herbals, Supplements, and Substances of Abuse – What Evidence Distinguishes Therapeutic from Adverse Responses?

6.1 Introduction

6.2 Summary and Conclusions

References

Chapter 7: Voluntary Exposures: Pharmaceutical Chemicals in Prescription and Over-the-Counter Drugs – Passing the Testing Gauntlet

7.1 Introduction

7.2 Testing of New Drug Entities for Genotoxicity

7.3 Relationship between Genotoxicity Testing and Rodent Carcinogenicity

7.4 Can Drug-Induced Human Cancer Be Predicted?

7.5 What Can Rodent Carcinogenicity Tell Us about Human Cancer Risk?

7.6 Genotoxicity Prediction Using “Traditional” In Silico Approaches

7.7 Covalent versus Noncovalent DNA Interaction

7.8 Use of New Technologies to Predict Toxicity and Cancer Risk: High-Throughput Methods

7.9 Transcriptomics

7.10 Single-Nucleotide Polymorphisms (SNPs)

7.11 Conclusions

Appendix A

References

Chapter 8: Children's and Adult Involuntary and Occupational Exposures and Cancer

8.1 Introduction

8.2 Occupational Exposures and Cancer

8.3 Environmental Exposures and Cancer

8.4 Conclusions and Future Perspectives

References

Part Three: Gene–Environment Interactions

Chapter 9: Ethnicity, Geographic Location, and Cancer

9.1 Introduction

9.2 Classification of Cancer

9.3 Ethnicity and Cancer

9.4 Geographic Location and Cancer

9.5 Ethnicity, Geographic Location, and Lung Cancer

9.6 Common Cancers in China

9.7 Cancer Risk Factors and Prevention

References

Chapter 10: Dietary/Supplemental Interventions and Personal Dietary Preferences for Cancer: Translational Toxicology Therapeutic Portfolio for Cancer Risk Reduction

10.1 Introduction

10.2 Gene Expression and Epigenetics

10.3 Environmental Lifestyle Factors Affecting Cancer Prevention and Risk

10.4 Dietary Patterns

10.5 Complementary and Integrative Oncology Interventions/Restorative Therapeutics

10.6 Special and Alternative Diets

10.7 Popular Anticancer Diets

10.8 Conclusion

Acknowledgment

References

Chapter 11: Social Determinants of Health and the Environmental Exposures: A Promising Partnership

11.1 Introduction

11.2 Social Determinants of Health

11.3 Conclusions: Social Determinants of Health and Windows of Susceptibility

Acknowledgments

References

Part Four: Categorical and Pleiotropic Nonmutagenic Modes of Action of Toxicants: Causality

Chapter 12: Bisphenol A and Nongenotoxic Drivers of Cancer

12.1 Introduction

12.2 Dosing

12.3 Receptor-mediated Signaling

12.4 Epigenetic Reprogramming

12.5 Oxidative Stress

12.6 Inflammation and Immune Response

12.7 BPA-Induced Carcinogenesis

12.8 Fresh Opportunities in BPA Research

References

Chapter 13: Toxicoepigenetics and Effects on Life Course Disease Susceptibility

13.1 Introduction to the Field of Toxicoepigenetics

13.2 Exposures that Influence the Epigenome

13.3 Intergenerational Exposures and Epigenetic Effects

13.4 Special Considerations and Future Directions for the Field of Toxicoepigenetics

13.5 Future Directions

13.6 Conclusions

Acknowledgments

References

Chapter 14: Tumor-Promoting/Associated Inflammation and the Microenvironment: A State of the Science and New Horizons

14.1 Introduction

14.2 The Immune System

14.3 Prioritized Chemicals

14.4 Experimental Models of Carcinogenesis through Inflammation and Immune System Deregulation

14.5 Antioxidants and Translational Opportunities

14.6 Tumor Control of the Microenvironment

Acknowledgments

References

Chapter 15: Metabolic Dysregulation in Environmental Carcinogenesis and Toxicology

15.1 Introduction

15.2 Metabolic Reprogramming and Dysregulation in Cancer

15.3 Moonlighting Functions

15.4 Cancer Metabolism in Context

15.5 Dual Roles for Metabolism in Both the Generation and Mitigation of Cellular Stress

15.6 Models of Carcinogenesis

15.7 Potential Metabolic Targets for Environmental Exposures

15.8 Metabolic Changes Associated with Exposures to Selected Agents

15.9 A Conceptual Overview of Traditional and Emerging Toxicological Approaches to the Problem of Cancer Metabolism: Implications for Future Research

15.10 The Nosology of Cancer and Cancer Development

15.11 Discussion

Acknowledgments

References

Part Five: Biomarkers for Detecting Premalignant Effects and Responses to Protective Therapies during Critical Windows of Development

Chapter 16: Circulating Molecular and Cellular Biomarkers in Cancer

16.1 Introduction

16.2 Proteins in Body Fluids: Potential Biomarkers

16.3 Circulating Cell-Free Nucleic Acids

16.4 Extracellular Vesicles: General Features

16.5 Circulating Tumor Cells

16.6 Conclusions

References

Chapter 17: Global Profiling Platforms and Data Integration to Inform Systems Biology and Translational Toxicology

17.1 Introduction

17.2 Global Omics Profiling Platforms

17.3 High-Throughput Bioactivity Profiling

17.4 Biomarkers

17.5 Exposomics

17.6 Bioinformatics to Support and Data Integration and Multiomics Efforts

17.7 Data Integration: Multiomics and High-Dimensional Biology Efforts

17.8 Conclusion

References

Chapter 18: Developing a Translational Toxicology Therapeutic Portfolio for Cancer Risk Reduction

18.1 Introduction

18.2 The Identification of Novel Predictors of Adverse Events

18.3 Proof of Principle Toxgnostics

18.4 Proposed Protocol

18.5 Fiscal Matters

18.6 The Future of Toxgnostics

References

Chapter 19: Ethical Considerations in Developing Strategies for Protecting Fetuses, Neonates, Children, and Adolescents from Exposures to Hazardous Environmental Agents

19.1 Introduction

19.2 What Is Ethics?

19.3 Ethical Considerations for Strategies Used to Protect Fetuses, Neonates, Children, and Adolescents from Exposures to Harmful Environmental Agents

19.4 Research with Human Participants

19.5 Conclusion

References

Index

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