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E-grāmata: Toxicogenomics-Based Cellular Models: Alternatives to Animal Testing for Safety Assessment

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Edited by (Professor and Chair, Department of Toxicogenomics, Maastricht University, the Netherlands)
  • Formāts: EPUB+DRM
  • Izdošanas datums: 02-Jan-2014
  • Izdevniecība: Academic Press Inc
  • Valoda: eng
  • ISBN-13: 9780123978714
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Toxicogenomics-Based Cellular Models: Alternatives to Animal Testing for Safety AssessmentPalielināt
  • Formāts: EPUB+DRM
  • Izdošanas datums: 02-Jan-2014
  • Izdevniecība: Academic Press Inc
  • Valoda: eng
  • ISBN-13: 9780123978714
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Researchers in genetics, toxicology, and other medical and public health specialties describe the current progress in developing toxicogenomics-based cellular models for chemical-induced carcinogenicity, immunotoxicity, and reproductive toxicity, all important endpoint of toxicity, the evaluation of which now costs large numbers of animal lives. They also introduce the field of toxicoinformatics, which deals with the big data generated by toxicogenomics technologies. Other areas covered are organ toxicity, selecting and validating toxicogenomic assays as alternatives to animal tests, and toxicogenomics implementation strategies. Annotation ©2014 Ringgold, Inc., Portland, OR (protoview.com)

Toxicogenomics-Based Cellular Models is a unique and valuable reference for all academic and professional researchers employing toxicogenomic methods with respect to animal testing for chemical safety. This resource offers cutting-edge information on the application of toxicogenomics to developing alternatives to current animal toxicity tests. By illustrating the development of toxicogenomics-based cellular models for critical endpoints of toxicity and providing real-world examples for validation and data analysis, this book provides an assessment of the current state of the field, as well as opportunities and challenges for the future. Written by renowned international toxicological experts, this book explores ‘omics technology for developing new assays for toxicity testing and safety assessment and provides the reader with a focused examination of alternative means to animal testing.

  • Describes the state-of-the-art in developing toxicogenomics-based cellular models for chemical-induced carcinogenicity, immunotoxicity, developmental toxicity, neurotoxicity and reproduction toxicity
  • Illustrates how to validate toxicogenomics-based alternative test models and provides an outlook to societal and economic implementation of these novel assays
  • Includes an overview of current testing methods and risk assessment frameworks
  • Provides a real-world assessment by articulating the current development and challenges in toxicogenomics while suggesting ways to move this field forward

Recenzijas

"Researchers in genetics, toxicology, and other medical and public health specialties describe the current progress in developing toxicogenomics-based cellular models for chemical-induced carcinogenicity, immunotoxicity, and reproductive toxicity, all important endpoint of toxicity, the evaluation of which now costs large numbers of animal lives." --ProtoView.com, April 2014

Papildus informācija

An authoritative resource based on real examples and current research for the application of toxicogenomics to developing alternatives to animal toxicity tests
List of Contributors xv
Section 1 Introduction To Toxicogenomics-Based Cellular Models
Chapter 1.1 Introduction to Toxicogenomics-Based Cellular Models
3(12)
Jos Kleinjans
1.1.1 The demands for alternatives to current animal test models for chemical safety
4(1)
1.1.2 The toxicogenomics approach
5(2)
1.1.3 Upgrading cellular models
7(1)
1.1.4 Regulatory aspects
8(2)
1.1.5 This book
10(1)
References
10(5)
Section 2 Genotoxicity And Carcinogenesis
Chapter 2.1 Application of In Vivo Genomics to the Prediction of Chemical-Induced (hepato)Carcinogenesis
15(20)
Scott S. Auerbach
Richard S. Paules
2.1.1 Introduction
15(2)
2.1.2 Toxicogenomics-based prediction of hepatocarcinogenic hazard
17(8)
In vivo studies in rats
17(7)
In vivo studies in mice
24(1)
2.1.3 Conclusion and future perspective
25(2)
References
27(8)
Chapter 2.2 Unraveling the DNA Damage Response Signaling Network Through RNA Interference Screening
35(22)
Louise von Stechow
Bob van de Water
Erik H.J. Danen
2.2.1 The DNA-damage-induced signaling response
35(3)
DNA damage sources and damage sensing
35(1)
Signal transduction in the DDR depends on a phosphorylation cascade
35(2)
The transcription factor p53 serves as a central hub in the cellular stress response
37(1)
p53 is regulated by posttranslational modifications
38(1)
2.2.2 DNA-damage-induced cellular responses
38(3)
DNA repair
38(1)
Repair of small DNA lesions
39(1)
Repair of bulky and helix-interfering DNA lesions
39(1)
DNA-damage-induced cell death
40(1)
DNA-damage-induced cell cycle arrest
41(1)
2.2.3 DNA damage in the context of cancer formation and treatment
41(2)
DNA damage and cancer formation
41(2)
Exploiting the DDR for improved cancer therapy
43(1)
2.2.4 RNAi screens to study the DDR signaling network
43(6)
Mechanism of RNA interference
43(1)
siRNA screening
44(1)
siRNA screens to study DDR signaling responses
45(1)
siRNA screens for identifying DNA-damage-induced cellular responses
46(1)
siRNA screens for identification of tumor-development-driving genes
47(1)
siRNA screening to identify novel cancer drug targets and synthetic lethal interactions
48(1)
siRNA screens to classify toxic compounds
48(1)
Outlook of siRNA screens
49(1)
References
49(8)
Section 3 Immunotoxicity
Chapter 3.1 Immunotoxicity Testing: Implementation of Mechanistic Understanding, Key Pathways of Toxicological Concern, and Components of These Pathways
57(10)
Erwin L. Roggen
Emanuela Corsini
Henk van Loveren
Robert Luebke
3.1.1 Introduction
57(1)
3.1.2 Animal-free assays to detect immunotoxicological endpoints
58(4)
Non-animal test methods for the identification of immunosuppressive chemicals
59(1)
Non-animal test methods for the identification of chemicals with the potential to induce skin sensitization
59(2)
Non-animal test methods for the identification of chemicals with the potential to induce respiratory sensitization
61(1)
3.1.3 Toxicogenomics approaches to predicting chemical safety
62(1)
3.1.4 Gaps and hurdles on the way to risk assessment and human safety
62(1)
3.1.5 An applied systems toxicology approach to predicting chemical safety
63(1)
References
64(3)
Chapter 3.2 Chemical Sensitization
67(22)
Marjam Alloul-Ramdhani
Cornelis P. Tensen
Abdoelwaheb El Ghalbzouri
3.2.1 Introduction
67(1)
3.2.2 Three-dimensional human skin equivalent as a tool for safety testing purposes
68(4)
Mimicking native human skin
69(1)
Skin barrier properties in human skin equivalents
70(1)
Validated safety tests using human skin equivalents
71(1)
3.2.3 Skin sensitization in keratinocytes
72(2)
Activation of the Keap1-Nrf2-ARE pathway by sensitizers
72(2)
Activation of Toll-like receptors by haptens in human keratinocytes
74(1)
Activation of the inflammasome by haptens in keratinocytes
74(1)
3.2.4 Toxicogenomic analysis of cutaneous responses
74(4)
Microarray-based gene expression analysis of human epidermal cells, in HSEs and ex vivo skin models
76(1)
Proteome analysis of human epidermal cells and in vivo/ex vivo skin
77(1)
3.2.5 Alternatives for animal testing of chemical sensitization: an overview
78(2)
References
80(9)
Chapter 3.3 'Omics-Based Testing for Direct Immunotoxicity
89(38)
Oscar L. Volger
3.3.1 Introduction to immunotoxicity
89(1)
3.3.2 Current guidelines for immunotoxicity testing
89(2)
3.3.3 Toxicogenomics
91(1)
The human transcriptome
92(1)
3.3.4 Transcriptome quantification tools
92(2)
Microarrays
92(1)
RNA sequencing
93(1)
3.3.5 Bioinformatics
94(5)
Quality control
94(1)
Statistics
95(1)
Classifier analyses
96(1)
Pathway analysis
97(1)
Toxicogenomics data infrastructure
98(1)
3.3.6 Immunotoxicogenomics studies: state of the art
99(11)
Human in vivo toxicogenomics studies
99(3)
Rodent in vivo toxicogenomics studies
102(2)
In vitro toxicogenomics studies
104(1)
Effect markers for direct immunotoxicity
104(3)
Molecular mechanisms of direct immunotoxicity
107(3)
3.3.7 Future directions
110(9)
Mechanisms of direct immunotoxicity
110(1)
In vivo validation of in vitro markers for immunotoxicity
110(1)
MOA and effect markers
110(1)
In vitro immunotoxicity testing for the registration of chemicals and drugs
111(1)
Novel tiered in vitro approach for immunotoxicity risk assessment
111(8)
References
119(8)
Section 4 Reproduction Toxicity
Chapter 4.1 Implementation of Transcriptomics in the Zebrafish Embryotoxicity Test
127(16)
Sanne A.B. Hermsen
Aldert H. Piersma
4.1.1 The zebrafish embryo as alternative test model for developmental toxicity testing
127(1)
4.1.2 The zebrafish embryotoxicity test-a variety of methods
127(1)
4.1.3 Developmental toxicity prediction using the zebrafish embryo
128(3)
4.1.4 ZET and toxicogenomics
131(1)
4.1.5 Concentration-dependent gene expression
132(1)
4.1.6 Relative embryotoxicity using gene expression data
133(1)
4.1.7 Identification of adaptive and adverse responses using transcriptomics
134(2)
4.1.8 Interspecies extrapolation of zebrafish gene expression data
136(1)
4.1.9 Future perspectives
136(2)
Improving the ZET-toxicokinetics
136(1)
Regulatory implementation
137(1)
References
138(5)
Chapter 4.2 Transcriptomic Approaches in In Vitro Developmental Toxicity Testing
143(16)
Elisa C.M. Tonk
Alden H. Piersma
4.2.1 Introduction to developmental toxicity testing
143(1)
4.2.2 Alternative models for developmental toxicity testing
144(1)
Whole-embryo culture
144(1)
Zebrafish
144(1)
Embryonic stem cells
145(1)
4.2.3 Application of transcriptomics in invitro developmental toxicity assessments
145(10)
Characterization
145(5)
Category approach
150(1)
Classification
151(1)
Comparisons across in vivo and in vitro models
151(4)
4.2.4 Outlook
155(1)
References
156(3)
Chapter 4.3 Thyroid Toxicogenomics: A Multi-Organ Paradigm
159(34)
Barae Jomaa
4.3.1 Introduction
159(2)
4.3.2 The thyroid system
161(1)
4.3.3 Mode-of-action-based alternative testing strategies for thyroid activity
161(19)
Primary effects on the thyroid system
165(5)
Secondary effects on the thyroid system
170(1)
Tertiary effects on the thyroid system
171(1)
Peripheral effects
172(2)
Hormone-kinetics-based effects
174(5)
Other MOAs affecting the thyroid hormone system
179(1)
4.3.4 Conclusion and future perspectives
180(1)
References
180(13)
Section 5 Organ Toxicity
Chapter 5.1 Hepatotoxicity Screening on In Vitro Models and the Role of 'Omics
193(20)
Joost van Delft
Karen Mathijs
Jan Polman
Maarten Coonen
Ewa Szalowska
Geert R. Verheyen
Freddy van Goethem
Marja Driessen
Leo van de Ven
Sreenivasa Ramaiahgari
Leo S. Price
5.1.1 General introduction to hepatotoxicity and its main pathologies
193(2)
Cholestasis
194(1)
Steatosis
194(1)
Necrosis
194(1)
5.1.2 'Omics-based in vitro approaches for hepatotoxicity screening: the NTC strategy
195(2)
Selection of compounds
195(1)
Toxicogenomics, metabolomics, and systems toxicology
195(2)
5.1.3 In vitro liver models used within NTC
197(6)
Immortalized cell lines
197(1)
3D cell models
198(2)
Primary mammalian hepatocytes
200(1)
Precision-cut liver slices
201(1)
Zebrafish embryos
202(1)
5.1.4 Non-'omics-based in vitro approaches for hepatotoxicity screening
203(3)
References
206(7)
Chapter 5.2 An Overview of Toxicogenomics Approaches to Mechanistically Understand and Predict Kidney Toxicity
213(22)
Giulia Benedetti
Bob van de Water
Marjo de Graauw
5.2.1 Brief introduction to toxicant-induced renal injury
213(4)
Renal morphology and physiology
213(1)
Pathophysiology of acute renal failure
213(1)
Nephrotoxic acute renal failure
214(1)
Role of inflammation in nephrotoxicity
214(3)
5.2.2 Use of toxicogenomics in kidney toxicity studies
217(10)
Transcriptomic strategies
217(5)
Proteomics strategies
222(2)
Metabolomics and metabonomics strategies
224(1)
Investigation of the role of the immune system in drug-induced organ toxicity by toxicogenomics
225(1)
Integration of toxicogenomics approaches
226(1)
5.2.3 Functional genomics: a new tool to study target organ toxicity
227(2)
Functional toxicogenomics in yeast
227(1)
RNAi screens in mammalian cells
227(2)
5.2.4 Conclusions
229(1)
References
229(6)
Chapter 5.3 'Omics in Organ Toxicity, Integrative Analysis Approaches, and Knowledge Generation
235(16)
Laura Suter-Dick
5.3.1 Introduction
235(2)
5.3.2 Gene-expression analysis in the identification of target organ toxicity
237(7)
Toxicogenomics: DBs
238(2)
Animal studies
240(2)
In vitro approaches
242(2)
5.3.3 Integration of gene-expression data with other 'omics technologies
244(1)
5.3.4 Systems toxicology approaches for biomarker discovery and mechanisms of toxicity
245(2)
5.3.5 miRNAs and organ toxicity: putative biomarkers of toxicological processes
247(1)
References
248(3)
Chapter 5.4 Hepatotoxicity and the Circadian Clock: A Timely Matter
251(22)
Annelieke S. de Wit
Romana Nijman
Eugin Destici
Ines Chaves
Gijsbertus T.J. van der Horst
5.4.1 Introduction
251(1)
5.4.2 The mammalian circadian clock
252(2)
The molecular clock
252(2)
Circadian clocks in peripheral tissues and cells
254(1)
5.4.3 Clock-controlled genes
254(1)
5.4.4 Metabolism and the circadian clock
255(4)
Liver metabolism and the circadian clock
255(1)
Xenobiotic metabolism and the circadian clock
256(1)
Aryl-hydrocarbon-receptor-dependent metabolism
257(2)
5.4.5 DNA damage and the circadian clock
259(1)
5.4.6 Chronotoxicity
259(1)
5.4.7 In vitro alternatives for toxicity testing
260(3)
The circadian clock and in vitro alternatives for hepatotoxic risk assessment
260(1)
In vitro chronotoxicity assays
261(2)
5.4.8 Concluding remarks
263(1)
Acknowledgments
263(1)
References
264(9)
Section 6 Toxicoinformatics
Chapter 6.1 Introduction to Toxicoinformatics
273(2)
Rob H. Stierum
References
274(1)
Chapter 6.2 Toxicogenomics and Systems Toxicology Databases and Resources: Chemical Effects in Biological Systems (CEBS) and Data Integration by Applying Models on Design and Safety (DIAMONDS)
275(16)
Jennifer Fostel
Eugene van Someren
Tessa Pronk
Jeroen Pennings
Peter Schmeits
Jia Shao
Dinant Kroese
Rob Stierum
6.2.1 Introduction
275(2)
6.2.2 Chemical effects in biological systems
277(6)
Components of a study in CEBS
277(1)
Data domains and data standardization
278(1)
Data integration
279(3)
Standards
282(1)
Minimal and "maximal" information about a study
282(1)
6.2.3 Data integration by applying models on design and safety (DIAMONDS)
283(7)
DIAMONDS-NTC infrastructure
283(1)
Navigation through the system
284(2)
DIAMONDS analysis: two examples
286(4)
References
290(1)
Chapter 6.3 Bioinformatics Methods for Interpreting Toxicogenomics Data: The Role of Text-Mining
291(16)
Kristina M. Hettne
Jos Kleinjans
Rob H. Stierum
Andre Boorsma
Jan A. Kors
6.3.1 Bioinformatics approaches to toxicogenomics data analysis
291(3)
Toxicological class discovery and separation
291(1)
Connectivity mapping
292(1)
Mechanistic analysis
292(1)
Identifying early predictors of toxicity
293(1)
6.3.2 Text-mining and its application in toxicogenomics
294(7)
Concept identification in free text
295(1)
Information extraction
296(1)
Literature-based discovery
297(1)
Assigning gene function: text-mining applied to gene-expression data
298(1)
Application in toxicogenomics
299(2)
References
301(6)
Section 7 Selection And Validation Of Toxicogenomics Assays As Alternatives To Animal Tests
Chapter 7.1 Selection and Validation of Toxicogenomics Assays as Alternatives to Animal Tests
307(14)
Bart van der Burg
Harrie Besselink
Bram Brouwer
7.1.1 Introduction: modern approaches in the development of animal alternatives
307(1)
7.1.2 Generic elements in the validation of alternative toxicity assays
308(1)
7.1.3 Stages in the process of development of validated tests
309(1)
7.1.4 Method validation in relation to its intended use
310(1)
Scientific research purposes
310(1)
Monitoring purposes
310(1)
Alternative, non-animal tests
311(1)
7.1.5 Generic bottlenecks in the validation process
311(1)
7.1.6 Feasibility: a practical approach to application
312(1)
7.1.7 Evaluation criteria for prioritization of scientific tools to enter a pre-validation process
312(2)
Criterion 1: scientific basis for predictability
313(1)
Criterion 2: single- vs multiple-target-type assays
313(1)
Criterion 3: (pre-)validation status of tools
313(1)
Criterion 4: technological and commercial feasibility aspects
314(1)
7.1.8 Validation of toxicogenomics assays
314(1)
7.1.9 Perspectives
315(1)
References
316(5)
Section 8 Toxicogenomics Implementation Strategies
Chapter 8.1 Toxicogenomics Implementation Strategies
321(16)
Wouter T.M. Jansen
Jan Hendrik R.H.M. Schretlen
8.1.1 Introduction
321(1)
8.1.2 The TGX market is driven by regulations
322(1)
8.1.3 The European TGX market is still latent
323(1)
8.1.4 The TGX market develops towards mechanistic understanding of the toxicology mode of action
323(1)
8.1.5 The best market segments for TGX product/service providers are pharmaceutical and cosmetics companies
324(2)
Nutritionals
324(1)
Chemicals
324(1)
Pharma
324(1)
Cosmetics
325(1)
Other markets and industries
325(1)
8.1.6 Validated predictive and mechanistic toxicology assays and data-analysis/interpretation services
326(2)
Predictive assays
326(1)
Carcinogenicity predictive assays
327(1)
Teratogenicity and immunogenicity predictive assays
327(1)
Mechanistic research
327(1)
Mechanistic assays
328(1)
Commercial data analysis and interpretation
328(1)
8.1.7 Competitors
328(1)
8.1.8 Investments
329(2)
Mechanistic assays
329(1)
Predictive assays
329(1)
Data analysis and interpretation
330(1)
8.1.9 Revenues
331(3)
Individual market volumes
331(1)
Cost savings
332(2)
8.1.10 Portfolio management
334(2)
The validation process is crucial to enter the market
334(1)
Human vs rodent TGX assays
334(1)
Cell-based reporter gene assays
335(1)
Cell-based mechanistic assays
335(1)
Cell-based assays facilitate bridging the cross-species barrier
335(1)
8.1.11 Conclusion
336(1)
References
336(1)
Index 337
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