The Chemical Biology of DNA Damage

 
 
Wiley-VCH (Verlag)
  • erschienen am 5. August 2011
  • |
  • XXII, 449 Seiten
 
E-Book | ePUB mit Adobe DRM | Systemvoraussetzungen
978-3-527-64211-3 (ISBN)
 
Bringing the power of biochemical analysis to toxicology, this modern reference explains genotoxicity at the molecular level, showing the links between a DNA lesion and the resulting cellular or organismic response. Clearly divided into two main sections, Part 1 focuses on selected examples of important DNA lesions and their biological impact, while the second part covers current advances in assessing and predicting the genotoxic effects of chemicals, taking into account the biological responses mediated by the DNA repair, replication and transcription machineries.
A ready reference for biochemists, toxicologists, molecular and cell biologists, and geneticists seeking a better understanding of the impact of chemicals on human health.
 
Das sehr moderne Handbuch bringt Aspekte der biochemischen Toxikologie, Molekularbiologie, Molekularmedizin und Umweltwissenschaft zusammen. Grundkonzepte werden besprochen, die Analyse und Vorhersage von Gentoxizität auf molekularer Ebene wird ausführlich erklärt.
1. Auflage
  • Englisch
  • 91
  • |
  • 4 s/w Tabellen, 19 farbige Abbildungen, 91 s/w Abbildungen
  • 5,67 MB
978-3-527-64211-3 (9783527642113)
3527642110 (3527642110)
weitere Ausgaben werden ermittelt
Nicholas E. Geacintov is Professor of Chemistry and former Chair of the Department of Chemistry at New York University (NYU), USA. He received his PhD degree in physical chemistry and polymer chemistry from the State University of New York College of Forestry at Syracuse University, and spent most of his career at NYU. His current research interests are focused on the mechanisms of chemical carcinogenesis and oxidatively generated DNA damage, especially the relationships between the structural features of DNA lesions and their impact on DNA repair and replication. He has published over 350 papers and is currently serving as a member of the Editorial Board of the Journal of Biological Chemistry.

Suse Broyde is Professor of Biology and Affiliate Professor of Chemistry at New York University, USA. Her research interests are focused on computer modeling of DNA lesions, with the goal of elucidating the molecular origins of their mutagenic and tumorigenic properties. She holds a PhD degree in physical chemistry with a minor in physics from the Polytechnic Institute of New York, and has published over 160 papers in peer-reviewed journals. She has been a member of the Editorial Advisory Board of Chemical Research in Toxicology.
Preface

PART I: Chemistry and Biology of DNA Lesions

INTRODUCTION AND PERSPECTIVES ON THE CHEMISTRY AND BIOLOGY OF DNA DAMAGE
Overview of the Field
DNA Damage ¿ A Constant Threat
DNA Damage and Disease
DNA Damage and Chemotherapeutic Applications
The Cellular DNA Damage Response (DDR)
Repair Mechanisms that Remove DNA Lesions
Relationships between the Chemical, Structural, and Biological Features of DNA Lesions
CHEMISTRY OF INFLAMMATION AND DNA DAMAGE: BIOLOGICAL IMPACT OF REACTIVE NITROGEN SPECIES
Introduction
DNA Oxidation and Nitration
DNA Deamination
2¿-Deoxyribose Oxidation
Indirect Base Damage Caused by RNS
Conclusions
OXIDATIVELY GENERATED DAMAGE TO ISOLATED AND CELLULAR DNA
Introduction
Single Base Damage
Tandem Base Lesions
Hydroxyl Radical-Mediated 2-Deoxyribose Oxidation Reactions
Secondary Oxidation Reactions of Bases
Conslusions and Perspectives
ROLE OF FREE RADICAL REACTIONS IN THE FORMATION OF DNA DAMAGE
Introduction
Importance of Free Radical Reactions with DNA
Mechanisms of Product Formation
Biological Implications
DNA DAMAGE CAUSED BY ENDOGENOUSLY GENERATED PRODUCTS OF OXIDATIVE STRESS
Lipid Peroxidation
2¿-Deoxyribose Peroxidation
Reactions of MDA and Beta-Substituted Acroleins with DNA Bases
Stability of M1dG: Hydrolytic Ring-Opening and Reaction with Nucleophiles
Propano Adducts
Etheno Adducts
Mutagenicity of Peroxidation-Derived Adducts
Repair of DNA Damage
Assessment of DNA Damage
Conclusions
POLYCYCLIC AROMATIC HYDROCARBONS: MULTIPLE METABOLIC PATHWAYS AND THE DNA LESIONS FORMED
Introduction
Radical Cation Pathway
Diol Epoxides
PAH o-Quinones
Future Directions
AROMATIC AMINES AND HETEROCYCLIC AROMATIC AMINES: FROM TOBACCO SMOKE TO FOOD MUTAGENS
Introduction
Exposure and Cancer Epidemiology
Enzymes of Metabolic Activation and Genetic Polymorphisms
Reactivity of N-Hydroxy-AAs and N-Hydroxy-HAAs with DNA
Synthesis of AA-DNA and HAA-DNA Adducts
Biological Effects of AA-DNA and HAA-DNA Adducts
Biological Effects of AA-DNA and HAA-DNA Adducts
Bacterial Mutagenesis
Mammalian Mutagenesis
Mutagenesis in Transgenic Rodents
Genetic Alterations in Oncogenes and Tumor Suppressor Genes
AA-DNA and HAA-DNA Adduct Formation in Humans
Future Directions
GENOTOXIC ESTROGEN PATHWAY: ENDOGENOUS AND EQUINE ESTROGEN HORMONE REPLACEMENT THEORY
Risks of Estrogen Exposure
Mechanisms of Estrogen Carcinogenesis
Estrogen Receptor as a Trojan Horse (Combined Hormonal/Chemical Mechanism)
Conclusions and Future Directions

PART II: New Frontiers and Challenges: Understanding Structure-Function Relationships and Biological Activity

INTERSTRAND DNA CROSS-LINKING 1,N2-DEOXYGUANOSINE ADDUCTS DERIVED FROM ALPHA, BETA-UNSATURATED ALDEHYDES: STRUCTURE-FUNCTION RELATIONSHIPS
Introduction
Interstrand Cross-Linking Chemistry of the Gamma-OH-PdG Adduct (9)
Interstrand Cross-Linking by the Alpha-CH3-Yamma-OH-PG Adducts Derived from Crotonaldehyde
Interstrand Cross-Linking by 4-HNE
Carbinolamine Cross-Links Maintain Watson-Crick Base-Pairing
Role of DNA Sequence
Role of Stereochemistry in Modulating Cross-Linking
Biological Significance
Conclusions
STRUCTURE-FUNCTION CHARACTERISTICS OF AROMATIC AMINE-DNA ADDUCTS
Introduction
Major Conformational Motifs
Conformational Heterogeneity
Structures of DNA Lesion-DNA Polymerase Complexes
Conclusions
MECHANISMS OF BASE EXCISION REPAIR AND NUCLEOTIDE EXCISION REPAIR
General Features of Base Excision and Nucleotide Excision Repair
BER
NER
Conclusions
RECOGNITION AND REMOVAL UF BULKY DNA LESIONS BY THE NUCLEOTIDE EXCISION REPAIR SYSTEM
Introduction
Overview of Mammalian NER
Prokaryotic NER
Recognition of Bulky Lesions by Mammalian NER Factors
Bipartite Model of Mammalian NER and the Multipartite Model of Lesion Recognition
DNA Lesions Derived from the Reactions of PAH Diol Epoxides with DNA are Excellent Substrates for Probing the Mechanisms of NER
Multidisciplinary Approach Towards Investigating Structure-Function Relationships in the NER of Bulky PAH-DNA Adducts
Dependence of DNA Adduct Conformations and

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