High-Throughput Screening Methods in Toxicity Testing

by Steinberg, Pablo

• ISBN13: 9781118065631
• ISBN10: 1118065638
• Edition: 1st
• Format: Hardcover
• Copyright: 2013-03-18
• Publisher: Wiley

Summary

High-throughput assays are part of a paradigm shift, to more cost-effective and reliable methods, in the testing of chemical and drug safety. This book covers methods, data generation, data analysis, and applications in risk assessment for major toxicological assays to help toxicologists apply and understand the benefits and limits of high-throughput testing assays. Each chapter describes method principles and includes detailed information on data generation, data analysis, and applications in risk assessment. The topic is especially timely given Europes REACH legislation and the US National Research Council.

Author Biography

PABLO STEINBERG, PhD, is Full Professor for Food Toxicology and Replacement/Complementary Methods to Animal Testing as well as Director of the Institute for Food Toxicology and Analytical Chemistry at the University of Veterinary Medicine Hannover. Prior to that, Dr. Steinberg was director of the Institute of Nutritional Science at the University of Potsdam. He has also held research positions at the University of Mainz.

Table of Contents

PREFACE ix

CONTRIBUTORS xi

PART I GENERAL ASPECTS

1 ToxCast: Predicting Toxicity Potential Through High-Throughput
Bioactivity Profiling 3
Keith A. Houck, Ann M. Richard, Richard S. Judson, Matthew T. Martin, David M. Reif, and Imran Shah

2 High-Throughput Toxicity Testing in Drug Development: Aims, Strategies, and Novel Trends 33
Willem G.E.J. Schoonen, Walter M.A. Westerink, Femke M. van de Water, and Horbach G. Jean

3 Incorporating Human Dosimetry and Exposure Information with High-Throughput Screening Data in Chemical Toxicity Assessment 77
Barbara A. Wetmore and Russell S. Thomas

4 The Use of Human Embryonic Stem Cells in High-Throughput Toxicity Assays 97
Xin Huang, Dan-yan Zhu, and Yi-jia Lou

PART II HIGH-THROUGHPUT ASSAYS TO ASSESS DIFFERENT CYTOTOXICITY ENDPOINTS

5 High-Throughput Screening Assays for the Assessment of Cytotoxicity 109
Andrew L. Niles, Richard A. Moravec, Tracy J. Worzella, Nathan J. Evans, and Terry L. Riss

6 High-Throughput Flow Cytometry Analysis of Apoptosis 129
Francesca de Giorgi and Franc¸ois Ichas

7 High Content Imaging-Based Screening for Cellular Toxicity Pathways 143
Bram Herpers and Bob van de Water

8 The Keratinosens Assay: A High-Throughput Screening Assay to Assess Chemical Skin Sensitization 159
Andreas Natsch

9 High-Throughput Screening Assays to Assess Chemical Phototoxicity 177
Satomi Onoue, Yoshiki Seto, and Shizuo Yamada

PART III HIGH-THROUGHPUT ASSAYS TO ASSESS DNA DAMAGE AND CARCINOGENESIS

10 Ames IITM and Ames Liquid Format Mutagenicity Screening Assays 193
Kamala Pant

11 High-Throughput Bacterial Mutagenicity Testing: VitotoxTM Assay 213
Luc Verschaeve

12 Genotoxicity and Carcinogenicity: Regulatory and Novel Test Methods 233
Walter M.A. Westerink, Joe C.R. Stevenson, G. Jean Horbach, Femke M. van de Water, Beppy van de Waart, and Willem G.E.J. Schoonen

13 High-Throughput Genotoxicity Testing: The Greenscreen Assay 271
Jorg Blumel and Nadine Krause

14 High-Throughput Assays to Quantify the Formation of DNA Strand Breaks 285
Marýa Moreno-Villanueva and Alexander Burkle

15 High-Throughput Versions of the Comet Assay 295
Irene Witte and Andre Stang

16 Automated Soft Agar Colony Formation Assay for the High-Throughput Screening of Malignant Cell Transformation 309
Pablo Steinberg

17 High-Throughput Quantification of Morphologically Transformed Foci in Bhas 42 Cells (v-Ha-ras Transfected BALB/c 3T3) Using Spectrophotometry 317
Kiyoshi Sasaki, Ayako Sakai, and Noriho Tanaka

PART IV HIGH-THROUGHPUT ASSAYS TO ASSESS REPRODUCTIVE TOXICITY, CARDIOTOXICITY,
AND HAEMATOTOXICITY

18 ReProGlo: A New Stem-Cell-Based High-Throughput Assay to Predict the Embryotoxic Potential of Chemicals 343
Frederik Uibel and Michael Schwarz

19 Embryonic Stem Cell Test (EST): Molecular Endpoints Toward High-Throughput Analysis of Chemical Embryotoxic Potential 357
Peter T. Theunissen, Esther de Jong, Joshua F. Robinson, and Aldert H. Piersma

20 Zebrafish Development: High-Throughput Test Systems to Assess Developmental Toxicity 371
Stephanie Padilla

21 Single Cell Imaging Cytometry-Based High-Throughput Analysis of Drug-Induced Cardiotoxicity 385
Min Jung Kim and Joon Myong Song

22 High-Throughput Screening Assays to Evaluate the Cardiotoxic Potential of Drugs 403
Carl-Fredrik Mandenius and Thomas Meyer

23 High-Throughput Screening Assays to Evaluate the Hematotoxic Potential of Drugs 421
Caroline Haglund, Rolf Larsson, and Martin Hoglund

PART V HIGH-THROUGHPUT ASSAYS TO ASSESS DRUG METABOLISM AND RECEPTOR-RELATED TOXICITY

24 High-Throughput Enzyme Biocolloid Systems for Drug Metabolism and Genotoxicity Profiling Using LC–MS/MS 433
James F. Rusling and John Schenkman

25 Higher-Throughput Screening Methods to Identify Cytochrome P450 Inhibitors and Inducers: Current Applications and Practice 453
David M. Stresser and George Zhang

26 High-Throughput Yeast-Based Assays to Study Receptor-Mediated Toxicity 479
Johanna Rajasarkka and Marko Virta

27 Evaluating the Peroxisomal Phenotype in High Content Toxicity Profiling 501
Jonathan Z. Sexton and Kevin P. Williams

28 A Panel of Quantitative Calux R Reporter Gene Assays for Reliable High-Throughput Toxicity Screening of Chemicals and Complex Mixtures 519
Bart van der Burg, Sander van der Linden, Hai-yen Man, Roos Winter, Lydia Jonker, Barbara van Vugt-Lussenburg, and Abraham Brouwer

29 DR-Calux R : A High-Throughput Screening Assay for the Detection of Dioxin and Dioxin-Like Compounds in Food and Feed 533
Barbara van Vugt-Lussenburg, Harrie T. Besselink, Bart van der Burg, and Abraham Brouwer

INDEX 547