Tobacco Documents Online

cover TOBACCO AN D H EALTH A Comprehensive Research Study of The Relationship of Tobacco and Health American Medical Association Education and Research Foundation 11' U() 1;C, z~7 t-3 . 0072924 TIM

A comprehensive Program of Research on Tobacco and Health - devoted to determining which significant human ailments may be caused or aggravated by smoking, how they may be caused or aggravated, the particular element or elements that may be the causal or aggravating agents and methods for eliminating such agents. T 001 sc.-IS :.7 TI1V11v 0072925

TOBACCO AND HEALTH Edited by Paul S. Larson, Ph.D., Chairman Department of Pharmacology Medical College Virginia 1976 American Medical Association Education and Research Foundation ~ w i :~:Z3 Y.) TIMN 0072926

Copyright (c) 1977 by American Medical Association Education and Research Foundation No part of this book may be reproduced in any form, by photostat, microfilm, duplicating machine or any other means, without the written permission of the publisher. American Medical Association Education and Research Foundation 535 North Dearborn Street Chicago, Illinois 505 10 T o0l .G-1a I I IMN o072927 T

PREFACE rI In January of 1964, the American Medical Association Education and Research Foundation (AMA-ERF) entered into a five year contract with six United States Tobacco companies' to conduct a comprehensive program of research on Tobacco and Health. The research was to be devoted primarily to determine which significant human ailments may be caused or aggravated by smoking, how they may be caused, the particular element or elements that may be the causal or aggravating agents and methods for eliminating such agents. The five participating tobacco companies pledged to contribute a total of ten million dollars to the AMA-ERF to finance this five year research effort. The AMA-ERF Board of Directors appointed an eminently qualified Advisory Committee2 to develop guidelines and suggestions on research policies and procedures, identify significant areas of research and screen applications for research gran ts. This contract was renewed in 1969 for another five years, terminating in August 1976. On July 18, 1972, the contract was altered to eliminate industy's financial commitment in 1972 and 1973 with no new grant applications being accepted :in 1973 although grants funded in 1972 were to be continued to completion. Between 1964 and 1975, 84 United States and 17 foreign research institutions, involving 196 researchers, produced 799 abstracts on the relationship of tobacco and health on (1) Absortion, Distribution, Metabolism, Excretion and Toxicology; (2) Carcinogenesis; (3) Cardiovascular; (4) Central and Autonomic Nervous ;3ystem; (5) Gastrointestinal Tract; (6) Reproduction; and (7) Respiratory System. The content of this publication includes a summary of the research projects con- ducted in each of the above sections, abstracts of each of the 799 research projects and the names of the participating researchers. It is hoped that this information will stimu- late new research in the field of Tobacco and Health and serve to prevent duplication of research efforts already explored. The American Medical Association and its Education and Research Foundation wish to express its gratitude to the tobacco industry for its financial support, the members of the Scientific Advisory Committee, the participating institutions and the 195 researchers without whose dedication and intellect this book would not have been possible. ' The American Tobacco Company Brown and Williamson Tobacco Corporation Liggett and Myers Tobacco Company P. Lorillard Company Philip Morris Incorporated R. J. Reynolds Tobacco Company 2 See page - James H. Sammons, M. D. Executive Vice President American Medical Association Education and Research Foundation ~ U(11:~•11 TINVI pp'1292g

AMA-ERF COMMITTEE FOR RESEARCH ON TOBACCO AND HEALTH (Appointed June 1964 - All Members still serving December 1976) Maurice H. Seevers, M.D., Ph.D., Committee Chairman Chairman, Department of Pharmacology University of Michigan John B. Hickman, M. D. Chairman, Department of Internal Medicine University of Indiana Charles LeMaistre, M D. Professor of Internal Medicine Southwestern Medical School at Dallas Paul S. Larson, Ph.D. Chairman, Department of Pharmacology Medical College of Virginia Richard J. Bing, M. D. Chairman, Department of Medicine Wayne State University College of Medicine Three of the members served on the 1964 Study Committee on Smoking; of the Surgeon General of the United States Public Health Service. ~ 4()1 .CI.i;~ 1.3 TIMN 0072929

ADVISORY COMMITTEE STATEMENT 7 l;(>1 :gz•Z3 T1A'N 0072930

CONTENTS Preface Advisory Committee Membership Advisory Committee Statement Section I Introduction, Absorption, Distribution, Metabolism, Excretion and Toxicology Summary Abstracts 1-1 Effects of Cigarette, Cigar, and Pipe Smoking on Nicotine Excretion. The influence of Inhaling 1-2 Distribution of Nicotine in the Rat 1-3 Tissue Distribution of [3H] Nicotine in Dogs and Rhesus Monkeys 1-4 Distribution of Nicotine in Central Nervous System 1-5 Age Dependent Changes in Nicotine Distribution in the Brain of the Mouse 1-6 Lethal Brain Concentration of Nicotine in Mice of Different Ages 1-7 Accumulation of Nicotine in Pancreatic Islets and Calcitonin-Producing Cells in Mice and Chicks Demonstrated by Micro-and whole-Body autoradiography 1-8 Catechol-and Indolamines in Some Endrocine Cell Systems. An Autoradiographical Histochemical and Radioimmunological Study 1-9 Dependence of Nicotine-C1 ° Distribution and Movements upon pH in Frog Sartorius Muscle 1-10 Uptake and Distribution of Nicotine-14 C in Frog Rectus Abdominus Muscle 1-11 Placental Transfer and Distribution of Nicotine in the Pregnant Rhesus Monkey :7 TIMN 0072931

- 1-12 Protein Conformation in Biomembranes: Optical Rotation and Absorption of Membrane Suspensions (items 1-13 through 1-5 1 to be listed) Section II Carcinogenesis Summary Abstracts (items 2-1 through 2-54 to be listed) 13 Section III Cardiovascular Summary Abstracts (items 3-1 through 3-297 to be listed) Section IV Central and Autonomic Nervous System Summary Abstracts (items 4-1 through 4-159 to be listed) Section V Gastrointestinal Tract Summary Abstracts (items 5-1 through 5-72 to be listed) Section VI Reproduction Summary Abstracts (items 6-1 through 6-47 to be listed) Section VII Respiratory System Summary Abstracts (items 7-1 through 7-174 to be listed) Authors Index Participating Institutions Index -r,wI.9.15 TIMN 0072932