Table Of ContentHandbook of
Teratology
4 Research Procedures
and Data Analysis
Handbook of Teratology
Volume 1: General Principles and Etiology
Volume 2: Mechanisms and Pathogenesis
Volume 3: Comparative, Maternal, and Epidemiologic Aspects
Volume 4: Research Procedures and Data Analysis
Handbook of
Teratology
Edited by
JAMES G. WILSON
The Children's Hospital Research Foundation
and Department of Pediatrics, University of Cincinnati
Cincinnati, Ohio
and
F. CLARKE FRASER
Departments of Biology and Paediatrics
McGI7.1 University and The Montreal Children's Hospital
Montreal, Canada
4 Research Procedures
and Data Analysis
PLENUM PRESS . NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Main entry under title:
Handbook of teratology.
Includes bibliographies and index.
CONTENTS: v. 1. General principles and etiology. - v. 2. Mechanisms and patho
genesis. - v. 3. Comparative, maternal, and epidemiologic aspects. - v. 4. Research
procedures and data analysis.
1. Deformities. 2. Teratogenic agents. I. Wilson, James Graves, 1915· II.
Fraser, F. Clarke, 1920- [DNLM: 1. Abnormalities. QS675 H236j
QM691.H26 616'.043 76-41787
ISBN· 13: 978'1'4615-8941'9 e·ISBN·13: 978-1-4615'8939-6
DOl: 10.1007/978-1-4615-8939'6
© 1978 Plenum Press, New York
Softcover reprint ofthe hardcover 1st edition 1978
A Division of Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted,
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission from the Publisher
Contributors
MASON BARR, JR., Department of Pediatrics, University of Michigan, Ann Arbor, Michigan
ROBERT L. BRENT, Departments of Pediatrics, Radiology, and Anatomy, Jefferson Medical
College, Philadelphia, Pennsylvania
THOMAS F. X. COLLINS, Division of Toxicology, Food and Drug Administration, Department
of Health, Education, and Welfare, Washington, D.C.
D. W. GAYLOR, National Center for Toxicological Research, Jefferson, Arkansas
MARCELA JENSEN, Jefferson Medical College, Stein Research Center, Philadelphia, Pennsyl
vania
HAROLD KALTER, Institute for Developmental Research, Children's Hospital Research Foun
dation, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincin
nati, Ohio
H. V. MALLING, Biochemical Genetics Section, Environmental Mutagenesis Branch, National
Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
MURIEL N. NESBITT, Department of Biology, University of California at San Diego, La Jolla,
California
D. A. T. NEW, Physiological Laboratory, Cambridge, England
A. K. PALMER, Huntingdon Research Centre, Huntingdon, Cambridgeshire, England
DONALD PIOUS, Division of Developmental Biology and Morphogenesis, Department of
Pediatrics, University of Washington, Seattle, Washington
EDMOND J. RITTER, Children's Hospital Research Foundation and Department of Pediatrics,
University of Cincinnati College of Medicine, Cincinnati, Ohio
PATRICIA M. RODIER, Department of Anatomy, School of Medicine, University of Virginia,
Charlottesville, Virginia
WILLIAM J. SCOTT, Children's Hospital Research Foundation and Department of Pediatrics,
University of Cincinnati College of Medicine, Cincinnati, Ohio
THOMAS H. SHEPARD, Central Laboratory for Human Embryology, Department of Pediat
rics, University of Washington, Seattle, Washington
JAMES G. WILSON, Children's Hospital Research Foundation and Department of Pediatrics,
University of Cincinnati College of Medicine, Cincinnati, Ohio
v
Contents
Section VIII:· Research Procedures and Data Analysis
I Techniques for Cytogenetic Analysis 3
MURIEL N. NESBITT
I. Introduction 3
II. Fetal Cultures 4
III. Cultures from Postnatal Stages 8
IV. Cultures from Peripheral Blood 10
V. Direct Preparations from Preimplantation Embryos 11
VI. Direct Preparations from Postimplantation Embryos 13
VII. Direct Preparations from Postnatal Stages 14
VIII. Staining and Banding Techniques 17
IX. Photography 20
X. Making the Karyotype 21
XI. Equipment and Reagents 28
References 31
2 Mutation Testing Systems 35
H. V. MALLING
I. Introduction 35
II. General Features of Testing Systems 36
III. Description of Individual Testing Systems 46
IV. Organization of Testing and Extrapolation to Man 59
V. Correlation among Mutagenicity, Carcinogenicity, and
Teratogenicity 63
VI. Where Do We Go from Here? 64
References 65
3 Cell, Tissue, and Organ Culture as Teratologic Tools 71
THOMAS H. SHEPARD AND DONALD PIOUS
I. Introduction 71
vii
viii CONTENTS
II. Methods 72
III. Teratological Utility of Culture Techniques 81
References 89
4 Whole Embryo Explants and Transplants 95
D.A.T.NEW
I. Introduction 95
II. Culture and Transfer Methods 96
III. Applications of Culture and Transfer Methods 108
IV. Assessment of Culture and Transfer Methods for Teratology
and Detection of Teratogenic Agents 125
References 128
5 Survey of in Vitro Systems: Their Potential Use in Teratogenicity
Screening 135
JAMES G. WILSON
I. Introduction 135
II. To Test or Not To Test 136
III. Appropriate Level of Biological Testing 139
IV. Review of Available in Vitro Systems 142
V. Concluding Comment 150
References 150
6 The Structure and Uses of Genetically Homogeneous Lines of
Animals 155
HAROLD KALTER
I. Introduction 155
II. The Genetics and Consequences of Inbreeding 156
III. The Genetic Purity of Inbred Strains 158
IV. Teratological Similarity of Subst rains 161
V. Variable Success in Inbreeding Different Species 164
VI. Uses of Homogeneous Lines 167
VII. Possible Disadvantages of Inbred Animals for Experimental
Teratology 176
VIII. Inbred Strain-Derived Hybrids in Teratology 179
IX. Selection in Teratology 180
X. Some Conclusions 181
References 181
7 Multigeneration Reproduction Studies 191
THOMAS F. X. COLLINS
I. Introduction 191
II. History 193
CONTENTS ix
III. Comparison to Single-Generation Study 195
IV. Specific Procedures 196
V. Test Compound 204
VI. Responses 205
VII. Statistical Analysis of Results 209
References 210
8 The Design of Subprimate Animal Studies 215
A. K. PALMER
I. Introduction 215
II. Materials 218
III. Choice of Species 219
IV. Dosages 229
V. Route of Administration 232
VI. Frequency of Administration 233
VII. Methods of Examination 234
VIII. Categorization and Definition of Abnormalities 239
IX. Number of Animals 241
X. Statistical Methods 242
XI. Assessment of Results 245
XII. Concluding Note 251
References 252
9 Feasibility and Design of Subhuman Primate Studies 255
JAMES G. WILSON
I. Introduction 255
II. Advantages of Primate Studies 257
III. Limitations of Primate Studies 261
IV. Design of Teratogenicity Studies Using Higher Nonhuman
Primates 263
V. Conclusions 269
References 270
10 Uterine Vascular Interruption and Combined Radiation and
Surgical Procedures 275
MASON BARR, JR., AND ROBERT L. BRENT
I. Uterine Vascular Interruption 275
II. Combined Radiation and Surgical Techniques 287
References 301
11 Analytical Techniques for the Study of Teratogenic
Mechanisms 305
EDMOND J. RITTER AND WILLIAM J. SCOTT
I. Introduction 305
x CONTENTS
II. Sample Preparation 306
III. Morphological Techniques 311
IV. Biochemical Assays 313
V. Assays for Drugs and Other Teratogenic Agents 323
References 329
12 Immunological Aspects of Development 339
ROBERT L. BRENT AND MARCELA JENSEN
I. Introduction 339
II. Studies with Nonmammalian Organisms 340
III. Studies with the Mammalian Organism 342
References 384
13 Behavioral Teratology 397
PATRICIA M. RODIER
I. Introduction 397
II. General Considerations 398
III. Some Behavioral Tests of Interest to Teratologists 407
IV. Conclusions 422
References 423
14 Methods and Concepts of Biometrics Applied to Teratology 429
D. W. GAYLOR
I. Introduction 429
II. Measures of Lethality 429
III. Measures of Teratogenic Effects 434
IV. Fetal Weight 435
V. Comparison of Control and Treated Groups 436
VI. Multiple-Dose Experiments: Dose-Response 444
References 444
Contents of the Complete Handbook (Volumes 1-4) 445
Index 449
