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ADVANCES IN Pharmacology and Chemotherapy VOLUME 7 ADVISORY BOARD D. BOVET Zstituto Superiore di Sanitb Rome, Italy B. B. BRODIE National Heart Institute Bethesda, Maryland J. H. BURN Oxford University Oxford, England J. F. DANIELLI Department of Biochemical Pharmacology School of Pharmacy State University of New York at Buffalo Buffalo, New York R. DOMENJOZ Pharmakologisches Znstitut Universitiit Bonn Bonn, Cfermany A. CARLSSON Department of Pharmacology University of Goteborg Goteborg,Sweden B. N. UPERN Ddpartement de Mddecine E xpdrimentale Coll8ge de France Paris, France K. K. CREN Department of Pharmacology University of Indiana Indianapolis, Indiana A. D. WELOH Squibb Institute for Medical Research New Brunswick, New Jersey ADVANCES IN Pharmacology and Chemotherapy EDITED BY Silvio Garattini A. Goldin Istituto di Ricerche Farmacologiche “Mario Negri” Milano, Italy National Cancer Institute Bethesda, Maryland F. Hawking 1. J. Kopin National Institute for Medical Research London, England National Institute of Mental Health Bethesda, Maryland VOLUME 7 ACADEMIC PRESS New York and London, 1969 COPYRIGHT @ 1969, BY ACADEMIC P R E S S , INC. ALL RIGHTS RESERVED NO PART O F THIS BOOK MAY B E REPRODUCED IN ANY FORM, BY PHOTOSTAT, MICROFILM, RETRIEVAL SYSTEM, OR ANY OTHER MEANS, WITHOUT WRITTEN PERMISSION FROM THE PUBLISHERS. ACADEMIC PRESS, INC. 111 Flfth Avenue, New Pork, New York 10003 United Kingdom Edition published by ACADEMIC PRESS, INC. (LONDON) LTD. Berkeley Square House, London WlX BBA LIBRARYOF CONGRESSCATALOGCARDNUMBER: 61-18298 PRINTED I N THE UNITED STATES O F AMERICA CONTRIBUTORS TO THIS VOLUME Numbers'in parentheses indicate the pages on which the authors' contributions begin. BETTY J. ABBOTT (1 17),Cancer Chemotherapy National Service Center, National Cancer Institute, National Institutes of Health, U.S. Public Health Service, Bethesda, Maryland RUBINBRESSLER (91),Departments of Medicine and Physiology and Pharmaw h y , Duke University Medical Center, Durham, North Carolina STANLEY G. BROWNE (211), Leprosy Study Centre, London, England H . 0. J. COLLIER(333), Department of Pharmacological Research, Division of Medical and Scientific Affairs, Parke-Davis and Company, Hounslow, Middlesex, England CARL-GUSTAFHAMMAR (53), Department of Toxicology, Swedish Medical Research Council, Karolinska Institutet, Stockholm, Sweden JONATHAN L. HARTWELL (1 17), Cancer Chemotherapy National Service Center, National Cancer Institute, National Institutes of Health, U.S. Public Health Service, Bethesh, Maryland BO HOLMSTEDT (53), Department of Toxicology, Swedish Medical Research Council, Karolinska Institutet, Stockholm, Sweden ERNEST JAWETZ (253), Departments of Microbiology, Medicine, and Pediatrics, University of California Medical Center, San Francisco, California JOHNSTEPHEN KIZER(91), Departments of Medicine and Physiology and Pharmacology, Duke University Medical Center, Durham, North Carolina JAN-ERIK LINDOREN (53),Department of Toxiwlogy, Swedish Medical Research Council, Karolinska Institutet, Stockholm, Sweden JAMESA. MCFADZEAN (309), The Research Laboratories, May & Baker Ltd., Dagenham, Essex, England H . R. PERKINS (283),National Institute for Medical Research, London, England RICHARD THAM(53), Department of Toxicology, Swedish Medical Research Council, Karolinska Institutet, Stockholm, Sweden ELLIOTS. VESELL*( l ) ,Section on Pharmacogenetics, Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Bethesda, Maryland *Present address : Department of Pharmacology, Milton S. Hershey Medical Center, Pennsylvania State University