Advances in Molecular Toxicology (eBook)

Front Cover 1
Advances in Molecular toxicology 4
Copyright 5
Contents 6
Contributors 10
Editor's Preface 12
Chapter 1: Chapter one: Recent Developments in Mediterranean Harmful Algal Events 14
1. Introduction 15
2. Distribution of Algal Toxins in the Mediterranean Sea 21
3. Recent Insights into the Latest Mediterranean Toxic Outbreaks 31
4. Conclusions 45
References 46
Chapter 2: Mechanism of Fiber Carcinogenesis: From Extranuclear Target to Transforming Growth Factor Signaling Pathway 56
1. Introduction 57
2. Interaction Between Asbestos and Tobacco Smoke 58
3. Neoplastic Transformation as a Surrogate for In Vivo Carcinogenicity 58
4. Transformation Induction by Asbestos and Radon 58
5. Asbestos as a Gene and Chromosomal Mutagen 59
6. Role of Fiber Cell Interaction in Mediating Fiber Genotoxicity 61
7. Asbestos Fibers Induce ROS 62
8. Source of the Reactive Radical Species 62
9. Extranuclear Target in Fiber Genotoxicity 63
10. Mutagenicity of Crocidolite-Treated Cytoplasts 64
11. Transformation Studies with Human Epithelial Cells 64
12. Causally Linked Genes to Fiber Carcinogenesis 66
13. Ectopic Reexpression of betaigH3 Suppresses Tumorigenic Phenotype 67
14. Summary 67
Acknowledgments 68
References 68
Chapter 3: Applications of Quadrupole-Linear Ion Trap Mass Spectrometry to the Analysis of Reactive Metabolites in Drug Discovery and Development 72
1. Introduction 73
2. Reactive Metabolite Analysis in Drug Discovery and Development 74
3. Mass Spectrometry in Reactive Metabolite Analysis 78
4. Quadrupole-Linear Ion Trap Mass Spectrometry (Q-trap) in Reactive Metabolite Analysis 83
5. Examples of Using the Q-trap to Study Drug Bioactivation 95
6. Conclusions 104
References 105
Chapter 4: Molecular Aspects of Neurotoxins in Dopaminergic Neurons 112
1. Neurodegeneration of Dopaminergic Neurons 112
2. 6-Hydroxydopamine Neurotoxin 113
3. MPTP Neurotoxin 117
4. Aminochrome as Endogenous Neurotoxin 119
5. Neurotoxin Election to Use in Preclinical Parkinsonism 122
Acknowledgments 123
References 123
Chapter 5: Molecular Mechanisms of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone-Induced Lung Carcinogenesis 130
1. Introduction 131
2. Carcinogenesis 131
3. Metabolism 132
4. DNA Damage 137
5. Mutagenic Activity of NNK Metabolites 148
6. DNA Adduct Repair 150
7. Relative Role of ?-Hydroxylation Pathways in the Carcinogenic Properties of NNK 154
8. Co-Carcinogenic Activity of NNK and its Metabolites 157
9. Summary 160
Acknowledgments 161
References 162
Chapter 6: Disruption of Heme Synthesis by Polyhalogenated Aromatics 174
1. Introduction 175
2. Heme Synthesis and Disruption 177
3. Porphyria Caused by Polyhalogenated Aromatics 185
4. Mechanistic Hypotheses 198
5. Liver Injury, Cancer, and Porphyria 204
6. Summary 207
Acknowledgments 208
References 208
Chapter 7: Aristolochic Acid Nephropathy: An Environmental and Iatrogenic Disease 224
1. Introduction 224
2. Toxicity of Aristolochia 225
3. AA-I and AA-II 225
4. Chinese Herb Nephropathy 226
5. Endemic (Balkan) Nephropathy 227
6. AAN = BEN = CHN 228
7. Dose-Toxicity Relationship 228
8. Renal Histopathology 229
9. Proximal Tubular Function 229
10. Urothelial Cancer 230
11. AL-DNA Adducts 230
12. Mutational Signature of AAN 232
13. Genetic Considerations 232
14. AAN as an Iatrogenic Disease 233
Acknowledgments 235
References 235
Subject Index 242