Toxicological carcinogenesis / David B. Clayson.

Format:

Book

Author/Creator:

Clayson, D. B. (David Barringer)

Language:

English

Subjects (All):

Chemical carcinogenesis.

Environmental toxicology.

Health risk assessment.

Physical Description:

196 pages : illustrations ; 24 cm

Place of Publication:

Boca Raton, FL : Lewis Publishers, [2000]

Contents:

Chapter 1. Introduction: What Causes Cancer? 1

1.1 What Is Cancer? 2

1.2 What Causes Cancer? 3

Part I. Investigation of Cancer Causation

Chapter 2. Epidemiology

Studies of Cancer Causes in Humans 9

2.1 Case Reports 10

2.2 Descriptive Epidemiology 12

2.3 Case-Control Studies 13

2.4 Prospective or Cohort Studies 14

2.5 What Has Epidemiology Taught Us about Human Cancer? 15

2.6 Basic Data and Epidemiology of Human Disease 16

2.7 Strengths and Weaknesses of Epidemiology 17

Chapter 3. Standard Animal Bioassays for Carcinogens 19

3.1 Historical Aspects 20

3.2 Protocols for the Cancer Bioassay: Compromises Between Cost and Effectiveness 21

3.2.1 Number of Animals 21

3.2.2 Exposure Levels: The Maximum Tolerated Dose 21

3.2.3 Duration of the Bioassay 23

3.2.4 Choice of Appropriate Test Rodents 23

3.2.5 Other Factors 24

3.3 Animal Care 25

3.4 Postmortem Examination and Tissue Analysis 26

3.5 Other Bioassay Protocols 27

3.6 Good Laboratory Practices 28

3.7 Reflections: What Does the Rodent Bioassay Mean? 29

Chapter 4. Other Methods for the Identification of Carcinogens: Are They Quicker, Less Expensive, and as Reliable? 31

4.1 In Vitro Mutagenicity Tests 31

4.2 In Vivo Approaches 33

4.2.1 Classical Approaches 33

4.2.2 Initiation-Promotion Studies 34

4.2.3 Cancer Chemopreventive Agents 35

4.2.4 Use of Pretumorous Lesions 35

4.3 Structure-Activity Relationships 36

Part II. Possible Human Exposures to Carcinogens

Chapter 5. Exposure in the Workplace 39

5.1 Skin Cancer 40

5.2 Bladder Cancer 42

5.3 Occupational Lung Cancer 46

5.3.1 Asbestos 46

5.3.2 Mining 48

5.3.3 Chromium and Nickel 49

5.3.4 Other Factors 50

5.4 Leukemia 50

5.5 Angiosarcoma of the Liver 51

Chapter 6. Cigarette Smoking: A Modern Plague 55

6.1 Lung Cancer and Cigarette Smoking 55

6.2 What is It in Cigarette Smoke that Leads to Cancer? 58

6.3 Reduction of Cigarette-Smoking Mortality 60

Chapter 7. Diet and Nutrition 63

7.1 The Amount Eaten and Its Energy Content 64

7.1.1 Fats 66

7.1.2 Bran 67

7.2 Natural and Manmade Antioxidants 67

7.3 Rodent Carcinogens Naturally Present in Human Food 70

7.4 Mold Contamination 73

7.5 Cooking-Related Carcinogens and Mutagens 74

7.6 Manmade Food Contaminants 75

7.7 Food Additives 76

7.8 Gross Nutritional Variations 78

7.9 Overview: What Should We Eat? 78

Chapter 8. Pharmaceuticals 81

8.1 Analgesics and Folk Lore 81

8.2 Chlornaphazin (2-Haphthylamine Mustard): A Tragedy 82

8.3 Hormones and Cancer 83

8.3.1 Diethylstilbestrol in Pregnancy 83

8.3.2 Early Oral Contraceptives 84

8.3.3 Estrogens Following Menopause 85

8.4 Cancer Chemotherapy and Radiotherapy 85

8.4.1 Radiation 86

8.4.2 Radioisotopes 88

8.5 Laxatives 88

8.6 Parasitic Infection and Cancer 88

8.7 Folk Remedies 90

8.8 Drug Safety: The Current Position 91

Chapter 9. The General Environment 93

9.1 Point Emissions 94

9.2 Enclosed Spaces 96

9.3 Agricultural Chemicals 96

9.4 Water Quality 98

9.5 Air Quality 99

Chapter 10. Rodent Carcinogenesis Bioassay as a Predictor for Human Cancers 103

10.1 Chemical Structures of Carcinogens 104

10.1.1 Aromatic Amines and Related Chemicals 105

10.1.2 Polycyclic Aromatic Hydrocarbons 106

10.1.3 N-Nitrosamines 106

10.1.4 Biological Alkylating and Arylating Agents 107

10.1.5 Proto-epoxides 107

10.1.6 Chlorinated Hydrocarbons and Related Chemicals 107

10.1.7 Hydrazines and Hydrazides 108

10.1.8 Phenolic Antioxidants 108

10.2 Overview: The Many Gaps 108

10.3 Genotoxicity Tests and Species Differences 109

Part III. Reducing the Risk of Cancer

Chapter 11. Carcinogenesis Mechanisms 113

11.1 Stages in Cancer Development 113

11.2 Carcinogenesis Mechanisms 116

11.2.1 Conversion of Chemicals to Waste Products 116

11.2.2 Electrophile Generation 118

11.2.3 Oxidative Damage to DNA 121

11.2.3.1 Fats 122

11.2.3.2 Other Carcinogens Inducing Oxidative Damage 123

11.2.3.2.1 Butylated Hydroxyanisole (BHA) 123

11.2.3.2.2 Peroxisome Proliferators 125

11.2.3.2.3 Metals 125

11.2.4 Specific Protein Binding and Modification of DNA Expression 126

11.2.5 Cellular Proliferation: Selecting Appropriate Methods 127

11.2.6 DNA Replication and Cellular Proliferation in Carcinogenesis 130

11.2.7 Naturally Occurring Tumors as a Factor in Carcinogenesis 132

11.3 Utility of Mechanisms in Reaching Decisions about Carcinogens 134

Chapter 12. Carcinogenesis Risk Assessment 137

12.1 Historical Aspects and Default Assumptions 138

12.1.1 The Delaney Clause 138

12.1.2 Other Factors 138

12.1.3 Evidence Contradicting the Default Assumptions 139

12.1.4 Escape from Default Assumptions 143

12.2 Biological Factors Affecting Risk Assessment 145

12.2.1 Mutation 145

12.2.2 Cellular Proliferation 146

12.2.2.1 Cytotoxicity 147

12.2.2.2 Hormonal Actions 148

12.2.2.3 Naturally Occurring Tumors 149

12.3 Assembling Evidence for Risk Assessment 149

12.3.1 Multi-Agent Risk Assessment 150

12.3.2 Pharmaceuticals 150

Chapter 13. Legislation, Regulation, and Education 153

13.1 Cigarette Smoking 154

13.2 Chronic Alcoholism 156

13.3 Eating 157

13.4 The Environment 159

Chapter 14. Envoi: Major Goals of Research 161

14.1 Cancer Control: Today's Position 164

14.2 The Future: Where Should We Go Next? 165

14.2.1 More Rapid and Less Costly Identification of Chemical Carcinogens 166

14.2.2 Cancer Chemoprevention 167

14.3 Future Trends in Cancer Research 169.

Notes:

Includes bibliographical references (pages 173-185) and index.

ISBN:

1566705088

OCLC:

47013774