{"product_id":"translational-toxicology-and-therapeutics-9781119023609","title":"Translational Toxicology and Therapeutics","description":"\u003cb\u003eBook Synopsis\u003c\/b\u003e\u003cbr\u003e\u003cp\u003eWritten by leading research scientists, this book integrates current knowledge of toxicology and human health through coverage of environmental toxicants, genetic \/ epigenetic mechanisms, and carcinogenicity.\u003c\/p\u003e \u003cul\u003e \u003cli\u003eProvides information on lifestyle choices that can reduce cancer risk\u003c\/li\u003e \u003cli\u003eOffers a systematic approach to identify mutagenic, developmental and reproductive toxicants\u003c\/li\u003e \u003cli\u003eHelps readers develop new animal models and tests to assess toxic impacts of mutation and cancer on human health\u003c\/li\u003e \u003cli\u003eExplains specific cellular and molecular targets of known toxicants operating through genetic and epigenetic mechanisms\u003c\/li\u003e \u003c\/ul\u003e\u003cbr\u003e\u003cbr\u003e\u003cb\u003eTable of Contents\u003c\/b\u003e\u003cbr\u003e\u003cp\u003eList of Contributors xix\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart One Introduction: The Case for Concern about Mutation and Cancer Susceptibility during Critical\u003c\/b\u003e \u003cb\u003eWindows of Development and the Opportunity to Translate Toxicology into a Therapeutic Discipline 1\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e1 What Stressors Cause Cancer and When? 3\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eClaude L. Hughes and Michael D. Waters\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e1.1 Introduction 3\u003c\/p\u003e \u003cp\u003e1.1.1 General Information about Cancer 5\u003c\/p\u003e \u003cp\u003e1.1.2 Stressors and Adaptive Responses 8\u003c\/p\u003e \u003cp\u003e1.2 What Stressors Cause Cancer and When? 8\u003c\/p\u003e \u003cp\u003e1.2.1 Mutagenic MOAs 13\u003c\/p\u003e \u003cp\u003e1.2.1.1 DNA Repair 14\u003c\/p\u003e \u003cp\u003e1.2.2 Epigenetic MOAs 16\u003c\/p\u003e \u003cp\u003e1.2.3 Nongenotoxic Carcinogens, ROS, Obesity, Metabolic, Diet, Environment, Immune, Endocrine MOAs 20\u003c\/p\u003e \u003cp\u003e1.2.4 Tumor Microenvironment MOAs 25\u003c\/p\u003e \u003cp\u003e1.3 Relevance of Circulating Cancer Markers 26\u003c\/p\u003e \u003cp\u003e1.4 Potential Cancer Translational Toxicology Therapies 29\u003c\/p\u003e \u003cp\u003e1.4.1 Well-Established\/Repurposed Pharmaceuticals 31\u003c\/p\u003e \u003cp\u003e1.4.2 GRAS\/GRASE, Diet, and Nutraceuticals 34\u003c\/p\u003e \u003cp\u003e1.4.2.1 Suppression of Cell Proliferation and Induction of Cell Death 35\u003c\/p\u003e \u003cp\u003e1.4.2.2 Anti-Inflammatory Effects: Insights from Various Diseases 36\u003c\/p\u003e \u003cp\u003e1.4.2.3 Upregulation of Tumor Suppressor MicroRNAs 38\u003c\/p\u003e \u003cp\u003e1.4.2.4 Regulation of Oxidative Stress 38\u003c\/p\u003e \u003cp\u003e1.4.2.5 Activation of Signal Transduction Pathways 39\u003c\/p\u003e \u003cp\u003e1.4.2.6 Mitigating Inherited Deleterious Mutations 40\u003c\/p\u003e \u003cp\u003e1.4.2.7 Mitigating Adverse Epigenetic States 42\u003c\/p\u003e \u003cp\u003e1.4.2.8 Paradigm for Study of Cancer Chemoprevention 43\u003c\/p\u003e \u003cp\u003e1.5 Modeling and the Future 47\u003c\/p\u003e \u003cp\u003eReferences 51\u003c\/p\u003e \u003cp\u003e\u003cb\u003e2 What Mutagenic Events Contribute to Human Cancer and Genetic Disease? 61\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eMichael D. Waters\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e2.1 Introduction 61\u003c\/p\u003e \u003cp\u003e2.1.1 Childhood Cancer, Developmental Defects, and Adverse Reproductive Outcomes 62\u003c\/p\u003e \u003cp\u003e2.1.2 Newborn Screening for Genetic Disease 62\u003c\/p\u003e \u003cp\u003e2.1.3 Diagnosis of Genetic Disease 63\u003c\/p\u003e \u003cp\u003e2.1.4 Familial and Sporadic Cancer 65\u003c\/p\u003e \u003cp\u003e2.2 Genetic Damage from Environmental Agents 67\u003c\/p\u003e \u003cp\u003e2.3 Testing for Mutagenicity and Carcinogenicity 71\u003c\/p\u003e \u003cp\u003e2.4 Predictive Toxicogenomics for Carcinogenicity 73\u003c\/p\u003e \u003cp\u003e2.5 Germ Line Mutagenicity and Screening Tests 76\u003c\/p\u003e \u003cp\u003e2.6 Reproductive Toxicology Assays in the Assessment of Heritable Effects 80\u003c\/p\u003e \u003cp\u003e2.6.1 Segmented Reproductive Toxicity Study Designs 80\u003c\/p\u003e \u003cp\u003e2.6.2 Continuous Cycle Designs 81\u003c\/p\u003e \u003cp\u003e2.6.2.1 One-Generation Toxicity Study 81\u003c\/p\u003e \u003cp\u003e2.6.2.2 Repeat Dose Toxicity Studies 82\u003c\/p\u003e \u003cp\u003e2.7 Assays in Need of Further Development or Validation 82\u003c\/p\u003e \u003cp\u003e2.7.1 Transgenic Rodent Gene Mutation Reporter Assay 82\u003c\/p\u003e \u003cp\u003e2.7.2 Expanded Simple Tandem Repeat Assay 84\u003c\/p\u003e \u003cp\u003e2.7.3 Spermatid Micronucleus (MN) Assay 85\u003c\/p\u003e \u003cp\u003e2.7.4 Sperm Comet Assay 86\u003c\/p\u003e \u003cp\u003e2.7.5 Standardization of Sperm Chromatin Quality Assays 86\u003c\/p\u003e \u003cp\u003e2.8 New Technologies 87\u003c\/p\u003e \u003cp\u003e2.8.1 Copy Number Variants and Human Genetic Disease 87\u003c\/p\u003e \u003cp\u003e2.8.2 Next-Generation Whole Genome Sequencing 88\u003c\/p\u003e \u003cp\u003e2.8.3 High-Throughput Analysis of Egg Aneuploidy in C. elegans, and Other Alternative Assay Systems 90\u003c\/p\u003e \u003cp\u003e2.9 Endpoints Most Relevant to Human Genetic Risk 91\u003c\/p\u003e \u003cp\u003e2.10 Worldwide Regulatory Requirements for Germ Cell Testing 94\u003c\/p\u003e \u003cp\u003e2.11 Conclusion 95\u003c\/p\u003e \u003cp\u003eAcknowledgments 96\u003c\/p\u003e \u003cp\u003eReferences 96\u003c\/p\u003e \u003cp\u003e\u003cb\u003e3 Developmental Origins of Cancer 111\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSuryanarayana V. Vulimiri and John M. Rogers\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e3.1 Introduction 111\u003c\/p\u003e \u003cp\u003e3.2 Current Trends in Childhood Cancer 112\u003c\/p\u003e \u003cp\u003e3.3 Potential Mechanisms of Prenatal Cancer Induction 113\u003c\/p\u003e \u003cp\u003e3.4 Ontogeny of Xenobiotic Metabolizing Enzymes and DNA Repair Systems 113\u003c\/p\u003e \u003cp\u003e3.5 The Developmental Origins of Health and Disease (DOHaD) Theory 115\u003c\/p\u003e \u003cp\u003e3.6 Epigenetic Regulation during Development 115\u003c\/p\u003e \u003cp\u003e3.6.1 Critical Periods for Epigenetic Regulation 116\u003c\/p\u003e \u003cp\u003e3.7 Mechanisms of Cancer in Offspring from Paternal Exposures 117\u003c\/p\u003e \u003cp\u003e3.8 Parental Exposures Associated with Cancer in Offspring 118\u003c\/p\u003e \u003cp\u003e3.8.1 Radiation 118\u003c\/p\u003e \u003cp\u003e3.8.2 Diethylstilbestrol 119\u003c\/p\u003e \u003cp\u003e3.8.3 Tobacco Smoke 120\u003c\/p\u003e \u003cp\u003e3.8.4 Pesticides 122\u003c\/p\u003e \u003cp\u003e3.8.5 Arsenic 123\u003c\/p\u003e \u003cp\u003e3.9 Models for the Developmental Origins of Selected Cancers 124\u003c\/p\u003e \u003cp\u003e3.9.1 Breast Cancer 124\u003c\/p\u003e \u003cp\u003e3.9.2 Leukemia 127\u003c\/p\u003e \u003cp\u003e3.10 Public Health Agencies’ Views on Prenatal Exposures and Cancer Risk 129\u003c\/p\u003e \u003cp\u003e3.10.1 The United States Environmental Protection Agency (US EPA) 129\u003c\/p\u003e \u003cp\u003e3.10.2 The California Environmental Protection Agency (CalEPA) 131\u003c\/p\u003e \u003cp\u003e3.10.3 Washington State Department of Ecology (WA DoE) 133\u003c\/p\u003e \u003cp\u003e3.11 Conclusions 134\u003c\/p\u003e \u003cp\u003eAcknowledgment 135\u003c\/p\u003e \u003cp\u003eReferences 135\u003c\/p\u003e \u003cp\u003e\u003cb\u003e4 The Mechanistic Basis of Cancer Prevention 147\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eBernard W. Stewart\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e4.1 Introduction 147\u003c\/p\u003e \u003cp\u003e4.2 A Mechanistic Approach 147\u003c\/p\u003e \u003cp\u003e4.2.1 Specifying Carcinogens 148\u003c\/p\u003e \u003cp\u003e4.2.2 Cancer Risk Factors Without Carcinogen Specification 148\u003c\/p\u003e \u003cp\u003e4.3 Preventing Cancer Attributable to Known Carcinogens 149\u003c\/p\u003e \u003cp\u003e4.3.1 Involuntary Exposure 149\u003c\/p\u003e \u003cp\u003e4.3.1.1 Infectious Agents 149\u003c\/p\u003e \u003cp\u003e4.3.1.2 Occupation 150\u003c\/p\u003e \u003cp\u003e4.3.1.3 Drugs 151\u003c\/p\u003e \u003cp\u003e4.3.1.4 Pollution 152\u003c\/p\u003e \u003cp\u003e4.3.1.5 Dietary Carcinogens 152\u003c\/p\u003e \u003cp\u003e4.3.2 Tobacco Smoking 153\u003c\/p\u003e \u003cp\u003e4.3.2.1 Measures to Limit Availability and Promotion 154\u003c\/p\u003e \u003cp\u003e4.3.2.2 Product Labeling, Health Warnings, and Usage Restrictions 154\u003c\/p\u003e \u003cp\u003e4.3.2.3 Smoking Cessation 155\u003c\/p\u003e \u003cp\u003e4.3.3 Alcohol Drinking 155\u003c\/p\u003e \u003cp\u003e4.3.4 Solar and Ultraviolet Radiation 156\u003c\/p\u003e \u003cp\u003e4.4 Prevention Involving Complex Risk Factors 157\u003c\/p\u003e \u003cp\u003e4.4.1 Workplace Exposures 157\u003c\/p\u003e \u003cp\u003e4.4.2 Diet and Overweight\/Obesity 157\u003c\/p\u003e \u003cp\u003e4.5 Prevention Independent of Causative Agents or Risk Factors 158\u003c\/p\u003e \u003cp\u003e4.5.1 Screening 158\u003c\/p\u003e \u003cp\u003e4.5.2 Chemoprevention 159\u003c\/p\u003e \u003cp\u003e4.6 Conclusion 160\u003c\/p\u003e \u003cp\u003eReferences 160\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart Two Exposures that Could Alter the Risk of Cancer Occurrence, and Impact Its Indolent or\u003c\/b\u003e \u003cb\u003eAggressive Behavior and Progression Over Time 171\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e5 Diet Factors in Cancer Risk 173\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eLynnette R. Ferguson\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e5.1 Introduction 173\u003c\/p\u003e \u003cp\u003e5.2 Obesity 174\u003c\/p\u003e \u003cp\u003e5.3 Macronutrients 175\u003c\/p\u003e \u003cp\u003e5.3.1 Protein 176\u003c\/p\u003e \u003cp\u003e5.3.2 Lipids 177\u003c\/p\u003e \u003cp\u003e5.3.3 Carbohydrates 178\u003c\/p\u003e \u003cp\u003e5.4 Micronutrients 181\u003c\/p\u003e \u003cp\u003e5.4.1 Vitamins 181\u003c\/p\u003e \u003cp\u003e5.4.2 Minerals 184\u003c\/p\u003e \u003cp\u003e5.5 Phytochemicals 184\u003c\/p\u003e \u003cp\u003e5.5.1 Phytoestrogens 185\u003c\/p\u003e \u003cp\u003e5.5.2 Other Phytochemicals 186\u003c\/p\u003e \u003cp\u003e5.6 Conclusions 188\u003c\/p\u003e \u003cp\u003eReferences 188\u003c\/p\u003e \u003cp\u003e\u003cb\u003e6 Voluntary Exposures: Natural Herbals, Supplements, and Substances of Abuse – What Evidence\u003c\/b\u003e \u003cb\u003eDistinguishes Therapeutic from Adverse Responses? 199\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eEli P. Crapper, Kylie Wasser, Katelyn J. Foster, and Warren G. Foster\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e6.1 Introduction 199\u003c\/p\u003e \u003cp\u003e6.1.1 Alcohol 200\u003c\/p\u003e \u003cp\u003e6.1.2 Cigarette Smoking 201\u003c\/p\u003e \u003cp\u003e6.1.3 Herbals and Supplements 202\u003c\/p\u003e \u003cp\u003e6.1.3.1 Melatonin 202\u003c\/p\u003e \u003cp\u003e6.1.3.2 Resveratrol 204\u003c\/p\u003e \u003cp\u003e6.1.3.3 Dong Quai 205\u003c\/p\u003e \u003cp\u003e6.1.3.4 Eleutherococcus 206\u003c\/p\u003e \u003cp\u003e6.1.3.5 Saw Palmetto 206\u003c\/p\u003e \u003cp\u003e6.1.3.6 Stinging Nettle 207\u003c\/p\u003e \u003cp\u003e6.2 Summary and Conclusions 207\u003c\/p\u003e \u003cp\u003eReferences 207\u003c\/p\u003e \u003cp\u003e\u003cb\u003e7 Voluntary Exposures: Pharmaceutical Chemicals in Prescription and Over-the-Counter Drugs – Passing the Testing Gauntlet 213\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eRonald D. Snyder\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e7.1 Introduction 213\u003c\/p\u003e \u003cp\u003e7.2 Testing of New Drug Entities for Genotoxicity 214\u003c\/p\u003e \u003cp\u003e7.3 Relationship between Genotoxicity Testing and Rodent Carcinogenicity 217\u003c\/p\u003e \u003cp\u003e7.4 Can Drug-Induced Human Cancer Be Predicted? 218\u003c\/p\u003e \u003cp\u003e7.5 What Can Rodent Carcinogenicity Tell Us about Human Cancer Risk? 220\u003c\/p\u003e \u003cp\u003e7.6 Genotoxicity Prediction Using “Traditional” In Silico Approaches 222\u003c\/p\u003e \u003cp\u003e7.7 Covalent versus Noncovalent DNA Interaction 223\u003c\/p\u003e \u003cp\u003e7.8 Use of New Technologies to Predict Toxicity and Cancer Risk: High-Throughput Methods 224\u003c\/p\u003e \u003cp\u003e7.9 Transcriptomics 225\u003c\/p\u003e \u003cp\u003e7.10 Single-Nucleotide Polymorphisms (SNPs) 226\u003c\/p\u003e \u003cp\u003e7.11 Conclusions 227\u003c\/p\u003e \u003cp\u003eAppendix A 228\u003c\/p\u003e \u003cp\u003eReferences 253\u003c\/p\u003e \u003cp\u003e\u003cb\u003e8 Children’s and Adult Involuntary and Occupational Exposures and Cancer 259\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eAnnamaria Colacci and Monica Vaccari\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e8.1 Introduction 259\u003c\/p\u003e \u003cp\u003e8.2 Occupational Exposures and Cancer 262\u003c\/p\u003e \u003cp\u003e8.2.1 Occupational Cancer in the Twenty-First Century 262\u003c\/p\u003e \u003cp\u003e8.2.2 Past and Present Occupational Exposure to Asbestos 263\u003c\/p\u003e \u003cp\u003e8.2.3 Toxicology of Fibers: What We Have Learned from the Asbestos Lesson 265\u003c\/p\u003e \u003cp\u003e8.2.3.1 Mechanism and Mode of Action of Asbestos and Asbestos-Like Fibers in Carcinogenesis: The Role of Inflammation and Immune System to Sustain the Cancer Process 268\u003c\/p\u003e \u003cp\u003e8.2.4 Occupational Exposures and Rare Tumors 270\u003c\/p\u003e \u003cp\u003e8.3 Environmental Exposures and Cancer 271\u003c\/p\u003e \u003cp\u003e8.3.1 Environmental Exposures and Disease: Is This the Pandemic of the Twenty-First Century? 271\u003c\/p\u003e \u003cp\u003e8.3.2 The Complexity of Environmental Exposures 272\u003c\/p\u003e \u003cp\u003e8.3.3 Environmental Impact on Early Stages of Life: Are Our Children at Risk? 274\u003c\/p\u003e \u003cp\u003e8.3.4 Environmental Endocrine Disruptors: The Steps Set Out to Recover Our Stolen Future 277\u003c\/p\u003e \u003cp\u003e8.3.5 From Occupational to Environmental Exposures: Asbestos and Other Chemicals of Concern 279\u003c\/p\u003e \u003cp\u003e8.3.5.1 Asbestos 279\u003c\/p\u003e \u003cp\u003e8.3.5.2 Arsenic and Arsenic Compounds 280\u003c\/p\u003e \u003cp\u003e8.3.5.3 Phthalates 282\u003c\/p\u003e \u003cp\u003e8.3.5.4 Pesticides 283\u003c\/p\u003e \u003cp\u003e8.3.5.5 Mycotoxins 286\u003c\/p\u003e \u003cp\u003e8.3.6 Air Pollution and Airborne Particulate Matter: The Paradigmatic Example of Environmental Mixtures 288\u003c\/p\u003e \u003cp\u003e8.3.6.1 Characteristics of PM and PM Exposures 289\u003c\/p\u003e \u003cp\u003e8.3.6.2 PM Exposures and Cancer 291\u003c\/p\u003e \u003cp\u003e8.3.6.3 Possible Mechanisms of PM Toxicity 293\u003c\/p\u003e \u003cp\u003e8.3.6.4 The Role of PM Exposures in the Fetal Origin of the Disease 294\u003c\/p\u003e \u003cp\u003e8.4 Conclusions and Future Perspectives 296\u003c\/p\u003e \u003cp\u003eReferences 299\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart Three Gene–Environment Interactions 317\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e9 Ethnicity, Geographic Location, and Cancer 319\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eFengyu Zhang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e9.1 Introduction 319\u003c\/p\u003e \u003cp\u003e9.2 Classification of Cancer 320\u003c\/p\u003e \u003cp\u003e9.2.1 Classification by Histology 320\u003c\/p\u003e \u003cp\u003e9.2.2 Classification by Primary Location 322\u003c\/p\u003e \u003cp\u003e9.3 Ethnicity and Cancer 323\u003c\/p\u003e \u003cp\u003e9.3.1 Cancer Death and Incidence 323\u003c\/p\u003e \u003cp\u003e9.3.2 Site-Specific Cancer Incidence 326\u003c\/p\u003e \u003cp\u003e9.3.3 Site-Specific Cancer Incidence between the United States and China 328\u003c\/p\u003e \u003cp\u003e9.4 Geographic Location and Cancer 331\u003c\/p\u003e \u003cp\u003e9.4.1 Mapping Human Diseases to Geographic Location 331\u003c\/p\u003e \u003cp\u003e9.4.2 Geographic Variation and Cancer in the United States 332\u003c\/p\u003e \u003cp\u003e9.5 Ethnicity, Geographic Location, and Lung Cancer 334\u003c\/p\u003e \u003cp\u003e9.5.1 Ethnic Differences 334\u003c\/p\u003e \u003cp\u003e9.5.2 Geographic Variation 335\u003c\/p\u003e \u003cp\u003e9.5.3 Individual Risk Factors 335\u003c\/p\u003e \u003cp\u003e9.6 Common Cancers in China 338\u003c\/p\u003e \u003cp\u003e9.6.1 Liver Cancer 339\u003c\/p\u003e \u003cp\u003e9.6.1.1 Geographic Variation 339\u003c\/p\u003e \u003cp\u003e9.6.1.2 Urban Residence and Sex 340\u003c\/p\u003e \u003cp\u003e9.6.1.3 Hepatitis B Virus Infection 340\u003c\/p\u003e \u003cp\u003e9.6.1.4 Familial Aggregation and Genetic Variants 341\u003c\/p\u003e \u003cp\u003e9.6.2 Gastric Cancer 342\u003c\/p\u003e \u003cp\u003e9.6.2.1 H. pylori 342\u003c\/p\u003e \u003cp\u003e9.6.2.2 Familial Aggregation 343\u003c\/p\u003e \u003cp\u003e9.6.2.3 Genetic Susceptibility Factors 343\u003c\/p\u003e \u003cp\u003e9.6.3 Esophageal Cancer 344\u003c\/p\u003e \u003cp\u003e9.6.3.1 Geographic Variation 344\u003c\/p\u003e \u003cp\u003e9.6.3.2 Viral Infections 344\u003c\/p\u003e \u003cp\u003e9.6.3.3 Familial Aggregation 345\u003c\/p\u003e \u003cp\u003e9.6.3.4 Genetic Susceptibility Factors 345\u003c\/p\u003e \u003cp\u003e9.6.4 Lung Cancer 346\u003c\/p\u003e \u003cp\u003e9.6.5 Genetic Susceptibility Factors 347\u003c\/p\u003e \u003cp\u003e9.6.6 Cervical Cancer 348\u003c\/p\u003e \u003cp\u003e9.7 Cancer Risk Factors and Prevention 348\u003c\/p\u003e \u003cp\u003e9.7.1 Environmental Chemical Exposure 348\u003c\/p\u003e \u003cp\u003e9.7.2 Infectious Agents 349\u003c\/p\u003e \u003cp\u003e9.7.3 Psychosocial Stress and Social Network 349\u003c\/p\u003e \u003cp\u003e9.7.4 The Developmental Origin of Adult-Onset Cancer 350\u003c\/p\u003e \u003cp\u003e9.7.5 Cancer Prevention and Intervention 351\u003c\/p\u003e \u003cp\u003eReferences 353\u003c\/p\u003e \u003cp\u003e\u003cb\u003e10 Dietary\/Supplemental Interventions and Personal Dietary Preferences for Cancer: Translational\u003c\/b\u003e \u003cb\u003eToxicology Therapeutic Portfolio for Cancer Risk Reduction 363\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSandeep Kaur, Elaine Trujillo, and Harold Seifried\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e10.1 Introduction 363\u003c\/p\u003e \u003cp\u003e10.2 Gene Expression and Epigenetics 364\u003c\/p\u003e \u003cp\u003e10.3 Environmental Lifestyle Factors Affecting Cancer Prevention and Risk 366\u003c\/p\u003e \u003cp\u003e10.3.1 Obesity 366\u003c\/p\u003e \u003cp\u003e10.3.2 Weight Loss 368\u003c\/p\u003e \u003cp\u003e10.3.3 Physical Activity 369\u003c\/p\u003e \u003cp\u003e10.4 Dietary Patterns 370\u003c\/p\u003e \u003cp\u003e10.5 Complementary and Integrative Oncology Interventions\/Restorative Therapeutics 373\u003c\/p\u003e \u003cp\u003e10.6 Special and Alternative Diets 377\u003c\/p\u003e \u003cp\u003e10.7 Popular Anticancer Diets 378\u003c\/p\u003e \u003cp\u003e10.7.1 Macrobiotic Diet 378\u003c\/p\u003e \u003cp\u003e10.7.2 The Ketogenic Diet 382\u003c\/p\u003e \u003cp\u003e10.7.3 Fasting Diet 383\u003c\/p\u003e \u003cp\u003e10.8 Conclusion 384\u003c\/p\u003e \u003cp\u003eAcknowledgment 384\u003c\/p\u003e \u003cp\u003eReferences 385\u003c\/p\u003e \u003cp\u003e\u003cb\u003e11 Social Determinants of Health and the Environmental Exposures: A Promising Partnership 395\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eLauren Fordyce, David Berrigan, and Shobha Srinivasan\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e11.1 Introduction 395\u003c\/p\u003e \u003cp\u003e11.1.1 Conceptual Model 397\u003c\/p\u003e \u003cp\u003e11.1.2 Difference versus Disparity 398\u003c\/p\u003e \u003cp\u003e11.2 Social Determinants of Health 399\u003c\/p\u003e \u003cp\u003e11.2.1 Race\/Ethnicity 399\u003c\/p\u003e \u003cp\u003e11.2.2 Social Determinants of Health: “Place” and Its Correlates 402\u003c\/p\u003e \u003cp\u003e11.2.3 Gender and Sexuality 405\u003c\/p\u003e \u003cp\u003e11.3 Conclusions: Social Determinants of Health and Windows of\u003c\/p\u003e \u003cp\u003eSusceptibility 407\u003c\/p\u003e \u003cp\u003eAcknowledgments 408\u003c\/p\u003e \u003cp\u003eReferences 408\u003c\/p\u003e \u003cp\u003ePart Four Categorical and Pleiotropic Nonmutagenic Modes of Action of Toxicants: Causality 415\u003c\/p\u003e \u003cp\u003e\u003cb\u003e12 Bisphenol A and Nongenotoxic Drivers of Cancer 417\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eNatalie R. Gassman and Samuel H. Wilson\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e12.1 Introduction 417\u003c\/p\u003e \u003cp\u003e12.2 Dosing 420\u003c\/p\u003e \u003cp\u003e12.3 Receptor-mediated Signaling 421\u003c\/p\u003e \u003cp\u003e12.4 Epigenetic Reprogramming 422\u003c\/p\u003e \u003cp\u003e12.5 Oxidative stress 424\u003c\/p\u003e \u003cp\u003e12.6 Inflammation and Immune Response 425\u003c\/p\u003e \u003cp\u003e12.7 BPA-Induced Carcinogenesis 426\u003c\/p\u003e \u003cp\u003e12.8 Fresh Opportunities in BPA Research 428\u003c\/p\u003e \u003cp\u003eReferences 429\u003c\/p\u003e \u003cp\u003e\u003cb\u003e13 Toxicoepigenetics and Effects on Life Course Disease Susceptibility 439\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eLuke Montrose, Jaclyn M. Goodrich, and Dana C. Dolinoy\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e13.1 Introduction to the Field of Toxicoepigenetics 439\u003c\/p\u003e \u003cp\u003e13.1.1 The Epigenome 440\u003c\/p\u003e \u003cp\u003e13.1.2 Epigenetic Marks are Heritable and Reversible 440\u003c\/p\u003e \u003cp\u003e13.1.3 DNA Methylation 441\u003c\/p\u003e \u003cp\u003e13.1.4 Histone Modifications and Chromatin Packaging 442\u003c\/p\u003e \u003cp\u003e13.1.5 Noncoding RNAs 443\u003c\/p\u003e \u003cp\u003e13.1.6 Key Windows for Exposure-Related Epigenetic Changes 443\u003c\/p\u003e \u003cp\u003e13.1.7 Evaluation of Environmentally Induced Epigenetic Changes in Animal Models and Humans 444\u003c\/p\u003e \u003cp\u003e13.2 Exposures that Influence the Epigenome 444\u003c\/p\u003e \u003cp\u003e13.2.1 Air Pollution 445\u003c\/p\u003e \u003cp\u003e13.2.2 Metals 447\u003c\/p\u003e \u003cp\u003e13.2.3 Endocrine Disrupting Chemicals (EDCs) 448\u003c\/p\u003e \u003cp\u003e13.2.4 Diet 451\u003c\/p\u003e \u003cp\u003e13.2.5 Stress 453\u003c\/p\u003e \u003cp\u003e13.3 Intergenerational Exposures and Epigenetic Effects 454\u003c\/p\u003e \u003cp\u003e13.4 Special Considerations and Future Directions for the Field of Toxicoepigenetics 456\u003c\/p\u003e \u003cp\u003e13.4.1 Tissue Specificity 456\u003c\/p\u003e \u003cp\u003e13.4.2 The Dynamic Nature of DNA Methylation 458\u003c\/p\u003e \u003cp\u003e13.5 Future Directions 459\u003c\/p\u003e \u003cp\u003e13.6 Conclusions 460\u003c\/p\u003e \u003cp\u003eAcknowledgments 461\u003c\/p\u003e \u003cp\u003eReferences 461\u003c\/p\u003e \u003cp\u003e\u003cb\u003e14 Tumor-Promoting\/Associated Inflammation and the Microenvironment: A State of the Science and\u003c\/b\u003e \u003cb\u003eNew Horizons 473\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eWilliam H. Bisson, Amedeo Amedei, Lorenzo Memeo, Stefano Forte, and Dean W. Felsher\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e14.1 Introduction 473\u003c\/p\u003e \u003cp\u003e14.2 The Immune System 475\u003c\/p\u003e \u003cp\u003e14.2.1 Innate Immune Response 475\u003c\/p\u003e \u003cp\u003e14.2.2 Adaptive Immune Response 478\u003c\/p\u003e \u003cp\u003e14.3 Prioritized Chemicals 482\u003c\/p\u003e \u003cp\u003e14.3.1 Bisphenol A 482\u003c\/p\u003e \u003cp\u003e14.3.2 Polybrominated Diphenyl Ethers 483\u003c\/p\u003e \u003cp\u003e14.3.3 4-Nonylphenol 485\u003c\/p\u003e \u003cp\u003e14.3.4 Atrazine 485\u003c\/p\u003e \u003cp\u003e14.3.5 Phthalates 486\u003c\/p\u003e \u003cp\u003e14.4 Experimental Models of Carcinogenesis through Inflammation and Immune System Deregulation 487\u003c\/p\u003e \u003cp\u003e14.5 Antioxidants and Translational Opportunities 493\u003c\/p\u003e \u003cp\u003e14.6 Tumor Control of the Microenvironment 495\u003c\/p\u003e \u003cp\u003eAcknowledgments 497\u003c\/p\u003e \u003cp\u003eReferences 497\u003c\/p\u003e \u003cp\u003e\u003cb\u003e15 Metabolic Dysregulation in Environmental Carcinogenesis and Toxicology 511\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eR. Brooks Robey\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e15.1 Introduction 511\u003c\/p\u003e \u003cp\u003e15.2 Metabolic Reprogramming and Dysregulation in Cancer 513\u003c\/p\u003e \u003cp\u003e15.2.1 Carbohydrate Metabolism in Cancer 515\u003c\/p\u003e \u003cp\u003e15.2.2 Lipid Metabolism in Cancer 519\u003c\/p\u003e \u003cp\u003e15.2.3 Protein Metabolism in Cancer 521\u003c\/p\u003e \u003cp\u003e15.3 Moonlighting Functions 523\u003c\/p\u003e \u003cp\u003e15.4 Cancer Metabolism in Context 523\u003c\/p\u003e \u003cp\u003e15.4.1 The Gestalt of Intermediary Metabolism 523\u003c\/p\u003e \u003cp\u003e15.4.2 Cancer Tissues, Cells, and Organelles as Open Systems 527\u003c\/p\u003e \u003cp\u003e15.4.3 The Endosymbiotic Nature of Cancer 527\u003c\/p\u003e \u003cp\u003e15.4.4 Catabolic and Anabolic Support of Cell Proliferation 528\u003c\/p\u003e \u003cp\u003e15.4.5 Cancer Heterogeneity 529\u003c\/p\u003e \u003cp\u003e15.4.6 Phenotypic Relationships between Cancer Cells and Their Parental Cell Origins 532\u003c\/p\u003e \u003cp\u003e15.4.7 Evolutionary Perspectives of Metabolic Fitness and Selection in Cancer Development 533\u003c\/p\u003e \u003cp\u003e15.5 Dual Roles for Metabolism in Both the Generation and Mitigation of Cellular Stress 536\u003c\/p\u003e \u003cp\u003e15.5.1 Metabolism and Oxidative Stress 537\u003c\/p\u003e \u003cp\u003e15.5.2 Metabolism and Hypoxic Stress 539\u003c\/p\u003e \u003cp\u003e15.5.3 Nutritional Stress and Metabolism 539\u003c\/p\u003e \u003cp\u003e15.5.4 Metabolism and Physical Stress 540\u003c\/p\u003e \u003cp\u003e15.5.5 Metabolism and Other Forms of Cellular Stress 541\u003c\/p\u003e \u003cp\u003e15.6 Models of Carcinogenesis 541\u003c\/p\u003e \u003cp\u003e15.6.1 Traditional Multistage Models of Cancer Development 542\u003c\/p\u003e \u003cp\u003e15.6.2 Role of Replicative Mutagenesis in Cancer Development 543\u003c\/p\u003e \u003cp\u003e15.6.3 Acquired Mismatch Model of Carcinogenesis 543\u003c\/p\u003e \u003cp\u003e15.7 Potential Metabolic Targets for Environmental Exposures 546\u003c\/p\u003e \u003cp\u003e15.7.1 Conceptual Overview of Potential Metabolic Targets 546\u003c\/p\u003e \u003cp\u003e15.7.2 Identification of Key Targetable Contributors to Metabolic Dysregulation and Selection 549\u003c\/p\u003e \u003cp\u003e15.7.2.1 Glycolysis 555\u003c\/p\u003e \u003cp\u003e15.7.2.2 Lipogenesis, Lipolysis, and the PPP 555\u003c\/p\u003e \u003cp\u003e15.7.2.3 Citric Acid Cycle 556\u003c\/p\u003e \u003cp\u003e15.7.2.4 Organizational or Compartmental Targets 556\u003c\/p\u003e \u003cp\u003e15.7.2.5 Metabolite Transport Mechanisms 557\u003c\/p\u003e \u003cp\u003e15.7.2.6 Signal Transduction Effectors 558\u003c\/p\u003e \u003cp\u003e15.8 Metabolic Changes Associated with Exposures to Selected Agents 559\u003c\/p\u003e \u003cp\u003e15.8.1 Selected Agents Classified by the World Health Organization’s International Agency for Research on Cancer (IARC) 559\u003c\/p\u003e \u003cp\u003e15.8.1.1 IARC Group 1 (Carcinogenic to Humans) 560\u003c\/p\u003e \u003cp\u003e15.8.1.2 IARC Group 2A (Probably Carcinogenic to Humans) 564\u003c\/p\u003e \u003cp\u003e15.8.1.3 IARC Group 2B (Possibly Carcinogenic to Humans) 565\u003c\/p\u003e \u003cp\u003e15.8.1.4 Other Agents 565\u003c\/p\u003e \u003cp\u003e15.8.2 Environmentally Relevant Combinatorial Exposures 567\u003c\/p\u003e \u003cp\u003e15.8.2.1 Occupational and Common Environmental Exposures 567\u003c\/p\u003e \u003cp\u003e15.8.2.2 Environmentally Relevant Low-Dose Combinatorial Exposures 568\u003c\/p\u003e \u003cp\u003e15.8.2.3 The Halifax Project 570\u003c\/p\u003e \u003cp\u003e15.9 A Conceptual Overview of Traditional and Emerging Toxicological Approaches to the Problem of Cancer Metabolism: Implications for Future Research 571\u003c\/p\u003e \u003cp\u003e15.9.1 General Experimental Considerations in the Study of Metabolism In Vitro 571\u003c\/p\u003e \u003cp\u003e15.9.2 Systems Biology and Current Approaches to In Vitro Toxicology Screening 573\u003c\/p\u003e \u003cp\u003e15.10 The Nosology of Cancer and Cancer Development 577\u003c\/p\u003e \u003cp\u003e15.11 Discussion 579\u003c\/p\u003e \u003cp\u003eAcknowledgments 583\u003c\/p\u003e \u003cp\u003eReferences 583\u003c\/p\u003e \u003cp\u003ePart Five Biomarkers for Detecting Premalignant Effects and Responses to Protective Therapies during Critical Windows of Development 607\u003c\/p\u003e \u003cp\u003e\u003cb\u003e16 Circulating Molecular and Cellular Biomarkers in Cancer 609\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eIlaria Chiodi, A. Ivana Scovassi, and Chiara Mondello\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e16.1 Introduction 609\u003c\/p\u003e \u003cp\u003e16.2 Proteins in Body Fluids: Potential Biomarkers 610\u003c\/p\u003e \u003cp\u003e16.2.1 Diagnostic Protein Biomarkers 612\u003c\/p\u003e \u003cp\u003e16.2.2 Prognostic Protein Biomarkers 613\u003c\/p\u003e \u003cp\u003e16.2.3 Protein Biomarkers of Drug Response 615\u003c\/p\u003e \u003cp\u003e16.3 Circulating Cell-Free Nucleic Acids 615\u003c\/p\u003e \u003cp\u003e16.3.1 Circulating Cell-Free Tumor DNA 616\u003c\/p\u003e \u003cp\u003e16.3.1.1 Cf-DNA Integrity, Microsatellite Instability, and LOH 617\u003c\/p\u003e \u003cp\u003e16.3.1.2 Tumor-Specific Genetic Alterations 617\u003c\/p\u003e \u003cp\u003e16.3.1.3 Tumor Genetic Alterations and Therapy Resistance 619\u003c\/p\u003e \u003cp\u003e16.3.1.4 Tumor Epigenetic Alterations: DNA Methylation 620\u003c\/p\u003e \u003cp\u003e16.3.2 Circulating Cell-Free RNA 621\u003c\/p\u003e \u003cp\u003e16.3.2.1 Circulating Cell-Free microRNA 621\u003c\/p\u003e \u003cp\u003e16.4 Extracellular Vesicles: General Features 624\u003c\/p\u003e \u003cp\u003e16.4.1 Classification of EVs 624\u003c\/p\u003e \u003cp\u003e16.4.2 EVs and Cancer 625\u003c\/p\u003e \u003cp\u003e16.4.3 EVs as Mediators of Cell-To-Cell Communication 627\u003c\/p\u003e \u003cp\u003e16.5 Circulating Tumor Cells 628\u003c\/p\u003e \u003cp\u003e16.5.1 Two-Step Processing of Blood Samples: Enrichment and Identification of Circulating Tumor Cells 628\u003c\/p\u003e \u003cp\u003e16.5.1.1 CTC Number as a Cancer Biomarker 630\u003c\/p\u003e \u003cp\u003e16.5.2 Characterization of CTCs 630\u003c\/p\u003e \u003cp\u003e16.5.2.1 Molecular Characterization of CTCs 630\u003c\/p\u003e \u003cp\u003e16.5.2.2 Functional Characterization of CTCs 632\u003c\/p\u003e \u003cp\u003e16.5.3 Single CTCs versus CTC Clusters 634\u003c\/p\u003e \u003cp\u003e16.5.4 In Hiding Before Getting Home, the Long Journey of CTCs 635\u003c\/p\u003e \u003cp\u003e16.6 Conclusions 635\u003c\/p\u003e \u003cp\u003eReferences 637\u003c\/p\u003e \u003cp\u003e\u003cb\u003e17 Global Profiling Platforms and Data Integration to Inform Systems Biology and Translational\u003c\/b\u003e \u003cb\u003eToxicology 657\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eBarbara A. Wetmore\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e17.1 Introduction 657\u003c\/p\u003e \u003cp\u003e17.2 Global Omics Profiling Platforms 659\u003c\/p\u003e \u003cp\u003e17.2.1 Genomics 659\u003c\/p\u003e \u003cp\u003e17.2.2 Epigenomics 661\u003c\/p\u003e \u003cp\u003e17.2.3 Transcriptomics 662\u003c\/p\u003e \u003cp\u003e17.2.4 Proteomics 665\u003c\/p\u003e \u003cp\u003e17.2.5 Metabolomics 668\u003c\/p\u003e \u003cp\u003e17.3 High-Throughput Bioactivity Profiling 669\u003c\/p\u003e \u003cp\u003e17.3.1 High-Throughput Bioactivity and Toxicity Screening 669\u003c\/p\u003e \u003cp\u003e17.3.2 In Vitro–In Vivo Extrapolation 671\u003c\/p\u003e \u003cp\u003e17.4 Biomarkers 672\u003c\/p\u003e \u003cp\u003e17.5 Exposomics 673\u003c\/p\u003e \u003cp\u003e17.6 Bioinformatics to Support and Data Integration and Multiomics Efforts 674\u003c\/p\u003e \u003cp\u003e17.7 Data Integration: Multiomics and High-Dimensional Biology Efforts 676\u003c\/p\u003e \u003cp\u003e17.8 Conclusion 679\u003c\/p\u003e \u003cp\u003eReferences 679\u003c\/p\u003e \u003cp\u003e\u003cb\u003e18 Developing a Translational Toxicology Therapeutic Portfolio for Cancer Risk Reduction 691\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eRebecca Johnson and David Kerr\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e18.1 Introduction 691\u003c\/p\u003e \u003cp\u003e18.2 The Identification of Novel Predictors of Adverse Events 693\u003c\/p\u003e \u003cp\u003e18.2.1 Candidate Gene Studies 693\u003c\/p\u003e \u003cp\u003e18.2.2 Genome-wide Associations 694\u003c\/p\u003e \u003cp\u003e18.2.3 Next-Generation Sequencing 695\u003c\/p\u003e \u003cp\u003e18.3 Proof of Principle Toxgnostics 696\u003c\/p\u003e \u003cp\u003e18.4 Proposed Protocol 698\u003c\/p\u003e \u003cp\u003e18.4.1 Integration within Randomized Control Trials 698\u003c\/p\u003e \u003cp\u003e18.4.2 Biobanking and Future-Proofing Samples 699\u003c\/p\u003e \u003cp\u003e18.4.3 Data Protection and Full Consent 702\u003c\/p\u003e \u003cp\u003e18.4.4 The Need for a Collaborative Approach 703\u003c\/p\u003e \u003cp\u003e18.4.5 Open Access to Results 704\u003c\/p\u003e \u003cp\u003e18.4.6 Translation from Bench to Bedside 705\u003c\/p\u003e \u003cp\u003e18.5 Fiscal Matters 706\u003c\/p\u003e \u003cp\u003e18.6 The Future of Toxgnostics 706\u003c\/p\u003e \u003cp\u003eReferences 707\u003c\/p\u003e \u003cp\u003e\u003cb\u003e19 Ethical Considerations in Developing Strategies for Protecting Fetuses, Neonates, Children, and\u003c\/b\u003e \u003cb\u003eAdolescents from Exposures to Hazardous Environmental Agents 711\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eDavid B. Resnik and Melissa J. Mills\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e19.1 Introduction 711\u003c\/p\u003e \u003cp\u003e19.2 What Is Ethics? 712\u003c\/p\u003e \u003cp\u003e19.2.1 Some Fundamental Ethical Values 712\u003c\/p\u003e \u003cp\u003e19.2.1.1 Benefits and Costs 712\u003c\/p\u003e \u003cp\u003e19.2.1.2 Individual Rights and Responsibilities 713\u003c\/p\u003e \u003cp\u003e19.2.1.3 Justice 713\u003c\/p\u003e \u003cp\u003e19.2.2 Value Conflicts and Ethical Decision-Making 713\u003c\/p\u003e \u003cp\u003e19.3 Ethical Considerations for Strategies Used to Protect Fetuses, Neonates, Children, and Adolescents from Exposures to Harmful Environmental Agents 715\u003c\/p\u003e \u003cp\u003e19.3.1 Education 715\u003c\/p\u003e \u003cp\u003e19.3.2 Testing\/Screening\/Monitoring 717\u003c\/p\u003e \u003cp\u003e19.3.3 Worker Protection 720\u003c\/p\u003e \u003cp\u003e19.3.4 Government Regulation 722\u003c\/p\u003e \u003cp\u003e19.3.5 Taxation 725\u003c\/p\u003e \u003cp\u003e19.3.6 Civil Liability 726\u003c\/p\u003e \u003cp\u003e19.3.7 Criminal Liability 729\u003c\/p\u003e \u003cp\u003e19.4 Research with Human Participants 730\u003c\/p\u003e \u003cp\u003e19.4.1 Return of Individualized Research Results 732\u003c\/p\u003e \u003cp\u003e19.4.2 Protecting Privacy and Confidentiality 733\u003c\/p\u003e \u003cp\u003e19.4.3 Interventional Studies 734\u003c\/p\u003e \u003cp\u003e19.4.4 Intentional Exposure Studies 736\u003c\/p\u003e \u003cp\u003e19.4.5 Protecting Vulnerable Participants 739\u003c\/p\u003e \u003cp\u003e19.5 Conclusion 742\u003c\/p\u003e \u003cp\u003eReferences 742\u003c\/p\u003e \u003cp\u003eIndex 751\u003c\/p\u003e","brand":"John Wiley \u0026 Sons Inc","offers":[{"title":"Default Title","offer_id":49406968562007,"sku":"9781119023609","price":176.36,"currency_code":"GBP","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0817\/1739\/5799\/files\/9781119023609.jpg?v=1730497731","url":"https:\/\/bookcurl.com\/products\/translational-toxicology-and-therapeutics-9781119023609","provider":"Book Curl","version":"1.0","type":"link"}