Research Procedures and Data Analysis PDF
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Handbook 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
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