Advances in Molecular Toxicology

Contributors

Preface

Chapter One. AHR- and ER-Mediated Toxicology and Chemoprevention

1 Introduction

2 AHR Ligands

3 Aryl Hydrocarbon Receptor

4 Estrogen Receptor α and β

5 Reciprocal AHR–ER Crosstalk

6 ERα-Dependent Regulation of AHR Action

7 Implications for Chemoprevention

8 Summary

References

Chapter Two. Free Radical Metabolites in Arylamine Toxicity

1 Introduction

2 Arylamine Toxicity

3 Arylamines to Nitroaromatics—Six Degrees of Redox Separation

4 Sources and Systems that Generate Free Radical Metabolites from Arylamine Xenobiotics

5 Reactions of Arylamine Radicals with Cellular Antioxidants

6 Reactions Between Arylamine Radicals and DNA

7 Arylamine Drugs and Blood Dyscrasias

8 Diverting Toxic Arylamine Free Radical Generation to Detoxification: Importance of Free Radical Targets

9 Mixtures Toxicology—Application to Arylamine Free Radicals

10 Protein Radicals and Toxicity—Future Prospects

11 Closing Remarks

References

Chapter Three. Genotoxicity of Polycyclic Aromatic Hydrocarbon Metabolites: Radical Cations and Ketones

1 Introduction

2 Exposure to PAHs

3 Exposure Risks of PAH

4 DNA Damage by PAH

5 PAH Metabolism to DNA-Reactive Metabolites

6 Diol-Epoxide Pathway

7 The Radical Cation Pathway

8 Depurinating PAH Adducts and AP Sites

9 Mutagenesis Studies to Address PAH Radical Cations

10 Evidence for AP Site Formation Due to Radical Cations

11 Mutagenicity Studies with B[a]P Radical Cation Products

12 The Quinone Pathway

13 Exposure to OPAHs

14 Biological Relevance of OPAH

15 Conclusion

References

Chapter Four. Nitrogen Oxides Toxicology of the Aerodigestive Tract

1 Introduction

2 Chemistry of Reactive Oxygen and Nitrogen Oxide Species and the Scavengers

3 Production of Reactive Oxygen and Nitrogen Oxide Species by Peroxidases

4 Production of Reactive Nitrogen Oxides Under the Conditions Simulating Dental Plaque

5 Production of Reactive Nitrogen Oxides in Acidified Plaque

6 Biochemical Symptoms of Periodontal Diseases

7 Functions of Salivary Nitrite and SCN⁻ in the Stomach

8 Concluding Remarks

References

Chapter Five. Noncholinesterase Protein Targets of Organophosphorus Pesticides

Abbreviations

1 Introduction

2 OP Nerve Agents and OP Pesticides

3 AChE: the Established Target of OP Toxicity

4 Neuropathy Target Esterase: an Established Target of OP Toxicity

5 OP Toxicity Targets in Addition to AChE

6 Metabolism of OP

7 In Vitro Studies Show OP Binding to Serine Hydrolases and to Receptors

8 Preliminary Identification of Serine Hydrolases as OP Targets in Mouse Brain

9 OP Binding to Proteins That Have No Active Site Serine

10 BChE, the Biomarker of Human Exposure to OP

11 Albumin, a Biomarker of OP Exposure in Humans

12 Mass Spectrometry Detection of OP Adducts on Albumin

13 Acylpeptide Hydrolase, a Potential Biomarker of OP Exposure

14 Future Directions

References

Chapter Six. Organophosphate Exposure: Detection and Remediation

1 Introduction

2 Mechanism of OP Toxicity to Humans

3 Detection of OP Exposure

4 Remediation of NA OP Poisoning

5 Future Directions and Challenges in OP Detection and Remediation

6 Conclusions

Acknowledgments

References

Index