High-Throughput Screening Methods in Toxicity Testing

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
Mar½a 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 LCâ"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