Chemical Induction of Cancer: Modulation and Combination Effects an Inventory of the Many Factors which Influence Carcinogenesis

729 Pages·1996·16.934 MB·English

by  Joseph C. Arcos, Mary F. Argus (auth.), Joseph C. Arcos, Mary F. Argus, Yin-tak Woo (eds.)

CHEMICAL INDUCTION
OF CANCER
CHEMICAL INDUCTION
OF CANCER
Modulation and Combination Effects
An Inventory of the Many Factors Which
Influence Carcinogenesis
Joseph C. Arcos
Editor
Mary F. Argus
Yin-tak Woo
Associate Editors
Birkhauser
Boston • Basel • Berlin
Joseph C. Arcos Yin-tak Woo
U.S. Environmental Protection Agency U.S. Environmental Protection Agency
Washington, D.C. 20460, USA Washington, D.C. 20460, USA
Tulane University School of Medicine
New Orleans, LA 70112, USA
Mary F. Argus This volume was produced under the
U.S. Environmental Protection Agency editorial coordination of
Washington, D.C. 20460, USA Harriet D. Shields
Tulane University School of Medicine Harriet Damon Shields & Associates
New Orleans, LA 70112, USA New York, NY 10010, USA
Library of Congress Cataloging-in-Publication Data
Chemical induction of cancer: modulation and combination effects: an
inventory of the many factors which influence carcinogenesis I
Joseph C. Arcos, editor; Mary F. Argus, Yin-tak Woo, associate
editors.
p. cm.
Includes bibliographical references and index.
ISBN-13: 978-1-4612-8640-0 e-ISBN-13: 978-1-4612-4076-1
001: 10.1007/978-1-4612-4076-1
1. Chemical carcinogenesis. 2. Cancer-Etiology. I. Arcos,
Joseph C. II. Argus, Mary F. III. Woo, Yin-tak.
[DNLM: 1. Neoplasms, Experimental-chemically induced.
2. Neoplasms-etiology. 3. Carcinogens. QZ 206 C516 1995]
RC268.6.C492 1995
616.88'4071-dc20
DNLM/DLC
for Library of Congress 94-29782
CIP
Printed on acid-free paper.
CI995 Birkhauser Boston
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This book provides a hitherto unavailable broad perspective on the complex causation of cancer, which
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ISBN 0-8176-3766-4 Typeset by TechType, Inc., Upper Saddle River, NJ
ISBN 3-7643-3766-4
987654321
This volume is dedicated
to
ERIC BOYLAND
ELIZABETH C. MILLER
and
JAMES A. MILLER
whose original and massive contributions
heralded the modern era
of chemical carcinogenesis research
and to
DIETRICH SCHMAHL
pioneer on combination effects
in carcinogenesis
Contents
Contributors xxiii
Acknowledgments xxvii
A Quote from 1962 xxix
Foreword by EMMANUEL FARBER xxxi
PREFATORY CHAPTER
Multifactor Interaction Network of Carcinogenesis
A "Tour Guide"
Joseph C. Arcos and Mary F. Argus
I. Introduction. The Interaction Network as a Graph 1
II. Review of Elements of the Network-An Analysis
of Their Interrelationships 2
A. Varieties of Initiation Processes 6
B. Beyond Initiation 8
C. Repositories of Inheritable Epigenetic Information 8
D. Role and Control of Mixed-Function Oxidases 10
E. Promoters versus Epigenetic Carcinogens 10
F. Promoters, Inhibitors, Calorie Intake versus Rate
of Cell Proliferation 11
G. The Neuroendocrine Interface. Factors Affecting
Hormonal Regulatory Pathways 11
H. Factors Affecting the Systemic Immune Network.
The Neuroimmunoendocrine Interface 12
I. Central Role of the Effect of Aging 13
J. Generation of Reactive Radical Species and Damage
to Membranes 14
K. Aging, Cancer, and Loss of Homeostatic Functions 14
III. Closing Note 15
References 16
vii
viii Contents
1
PART
Cross-Reactions between Carcinogens.
Modification of Chemical Carcinogenesis
by Noncarcinogenic Agents
CHAPTER 2
Synergism and Antagonism between Chemical Carcinogens
Martin R. Berger
I. Introduction 23
II. Sources and Selection of Data for Analysis 24
III. Overview of Carcinogenic Effects of Selected Binary Combinations 25
IV. Overview of Carcinogenic Effects of Selected Multiple (Nonbinary) Combinations of
Structurally-Defined Chemical Compounds and Complex Mixtures 36
V. Considerations on the Mechanisms Involved in the Synergistic and Antagonistic
Interactions of Chemical Carcinogens 45
References 48
CHAPTER 3
Synergism in Carcinogenesis: Mathematical Approaches
to Its Evaluation
Arnold E. Rei!
I. Theoretical Background 51
A. Conditions for Substantiation of Synergism 52
B. Classes of Synergism 52
1. Suggestion of Synergism 52
2. Apparent Synergism 52
3. Probable Synergism 53
4. Strict Synergism 53
5. Absolute Synergism 53
C. Significance of Linearity of Dose-Response Curves 54
D. Significance of Nonlinearity of Dose-Response Curves 54
E. Multiplicative Synergism 56
II. Examples of Substantiation of Classes of Synergism 58
A. Suggestion of Synergism (Class 1 Synergism) 58
B. Apparent Synergism (Class 2 Synergism) 58
C. Probable Synergism (Class 3 Synergism) 59
D. Strict Synergism (Class 4 Synergism) 60
E. Absolute Synergism (Class 5 Synergism) 60
III. Discussion 61
A. Definition and Statistical Considerations 61
B. On Interaction between Initiation and Promotion in Epidemiological Data 62
C. Some Principles of Testing for Synergism in Animals 62
D. Comments on Experimental Design of Testing for Synergism 63
E. Speculative Considerations on the Mechanism of Synergism 64
Appendix I: Statistical Significance 66
A. Significance of Linearity of Dose-Response Curves 66
Contents ix
B. Significance of Nonlinearity of Dose-Response Curves; Substantiation
of Strict Synergism 67
C. If Tumor Incidence in the Control Group Is Unknown 69
References 70
CHAPTER 4
Inhibition of Chemical Carcinogenesis
Gary J. KellofJ, Charles W. Boone, Vernon E. Steele, Judith R. Pay,
and Caroline C. Sigman
I. Introduction 73
II. Experimental Systems 74
III. Mechanisms of Inhibition 75
A. Blocking Activities 76
1. Inhibition of Carcinogen Uptake 76
2. Inhibition of the Formation or Activation of Carcinogens 78
3. Deactivation of Carcinogens 79
4. Increase of Detoxification by Enzymatic Reaction 79
5. Prevention of Carcinogen Binding to DNA 80
6. Increase of the Level or Fidelity of DNA Repair 80
B. Antioxidant Activities 81
1. Scavenging of Reactive Electrophiles 81
2. Scavenging of Oxygen Radicals 81
3. Inhibition of Arachidonic Acid (AA) Metabolism 83
C. Antiproliferative/A ntiprogression Activities 84
1. Modulation of Signal Transduction 84
2. Modulation of Hormonal/Growth Factor Activity 84
3. Inhibition of Oncogene Activity 85
4. Inhibition of Polyamine Metabolism 86
5. Induction of Terminal Differentiation 87
6. Restoration of Immune Response 87
7. Increasing Intercellular Communication 88
8. Restoration of Tumor-Suppressor Function 89
9. Induction of Programmed Cell Death (Apoptosis) 89
10. Correction of DNA Methylation Imbalance 90
11. Inhibition of Angiogenesis 90
12. Inhibition of Basement Membrane Degradation 91
13. Activation of Antimetastasis Genes 91
IV. Chemical Agents Classified by Structure or Biological Activity that Have
Displayed Inhibition of Chemical Carcinogenesis 91
A. Antihormones 92
B. Anti-inflammatory Agents 93
C. Antioxidants 93
D. Arachidonic Acid (AA) Metabolism Inhibitors 95
E. GSH Enhancers 96
F. Ornithine Decarboxylase (ODC) Inhibitors 97
G. Protein Kinase C (pKC) Inhibitors 98
H. Retinoids/Carotenoids 98
I. Thiols/Dithiolthiones/Sulfides 100
J. Other Chemical Classes Associated with Inhibition of Carcinogenesis 101
1. Arylalkyl Isothiocyanates 101
2. Calcium Compounds 103
3. DHEA/DHEA Analogs 104
4. Disulfiram/Disulfiram Analogs 104
x Contents
5. Glucarates 105
6. Indoles 105
7. Molybdenum Compounds 105
8. Monocyclic Terpenes/lsoprenylation Inhibiting Compounds 106
9. Protease Inhibitors 106
10. Selenium Compounds 106
11. Vitamin D3/Vitamin D3 Analogs 107
V. Cancer Chemoprevention: The Applied Science of the Inhibition
of Carcinogenesis 107
References 109
CHAPTER 5
Promotion and Cocarcinogenesis
INTRODUCTION 123
Friedrich Marks. Michael Schwarz. and Gerhard Furstenberger
SECTION I Tumor Promodon in Skin
Friedrich Marks and Gerhard Furstenberger
I. Multistage Carcinogenesis in Skin: Historical Background and
Basic Conceptual Developments 125
A. From Coal Tar Painting to the Initiation-Promotion Experiment 125
B. Initiation-Promotion in Mouse Skin: An Experimental Model 126
C. Conversion and Promotion ("Two-Stage Tumor Promotion'') 129
II. Skin Tumor Promoters 130
A. Tumor Promotion by Specific Interactions With Intracellular Signalling 130
B. Tumor Promotion via Nonspecific Tissue Damage 131
C. Skin Tumor Promoters Involved in the Etiology of Human Cancer 134
III. The Response of the Skin to Tumor Promoters 134
A. Tumor Development 134
1. Papillomas and Carcinomas 134
2. Species and Strain Differences 137
3. Tissue Specificity 138
B. Morphological and Cytological Responses 139
C. Biochemical Responses 140
1. Activation of Protein Kinase C 141
2. Effect on the Biosynthesis of Eicosanoids 141
3. Effect on the Generation of Reactive Oxygen Species 144
4. Induction of Ornithine Decarboxylase 145
IV. The Biological Nature of Skin Tumor Promotion and Conversion 145
A. Skin Tumor Promotion as the Consequence of a Chronic
Regenerative Reaction 146
B. Conversion and Wound Response 148
V. Concluding Remarks 150
References 151
SECTION II Tumor Promotion in Liver
Michael Schwarz
I. Stages in Hepatocarcinogenesis 161
II. Liver Tumor Promoters 161
III. Specificity of Liver Tumor Promoters 161
Contents xi
IV. Effectiveness of Promoter as Carcinogen Without Initiator;
Effect of Reversion of the Initiation-Promotion Sequence 163
V. Mechanisms of Tumor Promotion in Liver 165
A. Role of Liver Growth, Cell Proliferation, and Cell Death 165
B. Changes in Gap-Junction-Mediated Intercellular Communication 167
C. Role of Reactive Oxygen Species 169
VI. Quantitative Aspects of Tumor Promotion in Liver 170
VII. Relevance of Liver Tumor Promoters to Humans 172
References 173
SECTION IliA Note on Multistage Carcinogenesis in Other Organs
and In Vitro 180
Friedrich Marks
References 182
SECTION IIIB Note on Tumor Promoters, Cocarcinogens, and
N ongenotoxic Carcinogens 183
Friedrich Marks
References 184
CHAPTER 6
Computerized Data Management as a Tool to Study Combination
Effects in Carcinogenesis
Yin-tak Woo, Gregg Polansky, Joseph C. Arcos, Jeff Stokes DuBose,
and Mary F. Argus
I. Introduction 185
II. Combination Effects Categories: Definitions 186
III. Conceptual Principles Involved in the Development of ISS 187
A. The "Inherent Cancer Hazard" Component 187
B. The "Hazard Modification" Component 188
IV. System Overview and Application to Sample Mixtures 191
V. Closing Note 195
Appendix A: List of Structural and Functional Classes of Chemicals in ISS 197
Appendix B: Derivation of Class Hit Values (HB) as Inferences from Class Interactions 198
1. General Principles 198
2. The Class Pair Interaction Matrix 199
3. Absolute Cell Frequencies and Expected Cell Values lOO
4. Representativeness of Classes in the Database 201
5. Calculation of HB Values 201
6. Preparing an Inferred HB Values Class Matrix; the Use of These Values
in the Weighting Ratio 202
References 203
CHAPTER 7
Intercellular Communication: A Paradigm for the Interpretation of the
Initiation/Promotion/Progression Model of Carcinogenesis
James E. Trosko, Chia-Cheng Chang, Burra V. Madhukar, and Emmanuel Dupont
I. Introduction: Cancer as a Problem of Homeostatic Dysfunction 205
xii Contents
II. The Natural History of Carcinogenesis 106
III. Intercellular Communication: a Process to Ensure Homeostasis 210
IV. Dysfunctional Gap-Junctional Communication During Carcinogenesis 112
V. Chemical Inhibition During Tumor Promotion 213
VI. Oncogenes/Anti-Oncogenes or Tumor-Suppressor Genes
and Intercellular Communication 114
VII. Modulation of Gap-Junctional Intercellular Communication
by Growth Factors 216
VIII. Altered Gap Junction Function and "Partially Blocked Ontogeny"
During Carcinogenesis 116
IX. The Integration of Extracellular-Intracellular-Intercellular Communication
Mechanisms for Maintaining Homeostasis 118
X. Modulation of Gap-Junctional Communication and Its Implications
for the Prevention and Treatment of Cancer 220
References 221
APPENDIX TO PART 1
Chemical Cancerogenesis: Definitions of Frequently Used Terms
K. E. Appel, G. Fiirstenberger, H. J. Hapke, E. Hecker, A. G. Hildebrandt,
W. Koransky, F. Marks, H. G. Neumann, F. K. Ohnesorge, and R. Schulte-Hermann
I. Introduction 227
II. Definitions 117
A. Chemical Cancerogenesis 117
B. Chemical Risk Factors of Cancer 118
C. Solitary Cancerogeos (Synonyms: Cancerogens, Complete Cancerogens) 119
D. Conditional Cancerogens (Conditionally Cancer-Generating Factors) 229
E. Multistage Model of Cancerogenesis (Initiation, Promotion) 130
F. Progression 131
G. Cocancerogenesis 131
H. Syocancerogenesis 131
I. Anticancerogenesis 131
J. Syopromotion 131
K. Antipromotion 131
L. Genotoxicity 131
M. Threshold Values for Chemical Risk Factors of Cancer (Non-Observed
Effect Level, No-Effect Level, Threshold Value) 131
2
PART
Exogenous Factors and Endogenous Biological
Parameters That Modulate Chemical Carcinogenesis
CHAPTER 8
Immunotoxicology of Chemical Carcinogens
Karen A. Sullivan and John E. Salvaggio
I. Introduction 137
II. The Immune System 137
A. T Cells 138