Nutrients and Cancer Prevention Experimental Biology and Medicine Nutrients and Cancer Prevention, edited by Kedar N. Prasad and Frank L. Meyskens, Jr., 1990 Hepatic Encephalopathy, edited by Roger F. Butterworth and Gilles Pomier Layrargues, 1989 Molecular Actions of Alcohol, edited by Grace Y. Sun, P. Kevin Rudeen, W. Gibson Wood, Yau Huei Wei, and Albert Y. Sun, 1989 Epstein-Barr Virus and Human Disease • 1988, edited by D. V. Ablashi, A. Faggioni, G. R. F. Krueger, J. S. Pagano, and G. R. Pearson, 1989 Macromolecular Biorecognition, edited by Irwin Chaiken, Emilia Chiancone,Angelo Fontana, and Paolo Neri, 1987 Molecular Basis of Lymphokine Action, edited by David R. Webb, Carl W. Pierce, and Stanley Cohen, 1987 Biology of Copper Complexes, edited by John R. J. Sorenson, 1987 Epstein-Barr Virus and Human Disease, edited by P. H. Levine, D. V. Ablashi, M. Nonoyama, G. R. Pearson, and R. Glaser, 1987 Methods of Protein Sequence Analysis • 1986, edited by Kenneth A. Walsh, 1987 Regulation of Immune Gene Expression, edited by Marc Feldmann and Andrew McMichael, 1986 Biological Methylation and Drug Design, edited by Ronald T. Borchardt, Cyrus R. Creveling, and Per Magne Ueland, 1986 Retroviruses and Human Pathology, edited by Robert C. Gallo, Dominique Stehelin, and Oliviero E. Varnier, 1985 Directed Drug Delivery, edited by Ronald T. Borchardt, Arnold Repta, and Valentino Stella, 1985 Immune Regulation, edited by Marc Feldmann and N. A. Mitchison, 1985 Human T Cell Clones, edited by Marc Feldmann, Jonathan R. Lamb, and James N. Woody, 1985 Inositol and Phosphoinositides, edited by John E. Bleasdale, Joseph Eichberg, and George Hauser, 1985 Growth, Cancer, and the Cell Cycle, edited by Philip Skehan and Susan J. Friedman, 1984 Ir Genes, edited by Carl W. Pierce, Susan E. Cullen, Judith A. Kapp, Benjamin D. Schwartz, and Donald C. Shreffler, 1983 Methods in Protein Sequence Analysis, edited by Marshall Elzinga, 1982 Inflammatory Diseases and Copper, edited by John R. J. Sorenson, 1982 Nutrients and Cancer Prevention Edited by Kedar N. Prasad and Frank L. Meyskens, Jr. ~ Humana Press ~ Clifton, New Jersey Library of Congress Cataloging-in-Publication Data Nutrients and cancer prevention / edited by Kedar N. Prasad and Frank L. Meyskens, Jr. p. cm. - (Experimental biology and medicine) Based on the secontd meeting of the International Association for Vitamins and Nutritional Oncology, held in Charleston, S.c., June 25-29, 1989. sponsored by the Samuel Freeman Charitable Trust and others. Includes index. ISBN-13:978-1-4612-8856-5 e-ISBN-13:978-1-4612-4516-2 DOl: 10.10071978-1-4612-4516-2 1. Cancer-Surgery -Nu triional aspeets-Congresses. 2. Cancer -Prevention-Congresses. I. Prasad, Kedar N. II. Meyskens, F. L. (Frank L.) III. International Association for Vitamins and Nutritional Oncology, Meeting (2nd: 1989 : Charleston, S.c.) IV. Samuel Freeman Charitable Trust. V. Series: Experimental biology and medicine (aifion, N.J.) [DNLM: 1. ainical trials--congresses. 2. Neoplasms-prevention and control-rongresses. 3. Nutrition-rongresses. QZ 200 N9755 1989] RC268.45.N87 1990 616.99' 405-dc20 DNLM/DLC for Library of Congress 90-4677 CIP © 1990 The Humana Press Inc. Softcover reprint of the hardcover 1st edition 1990 Crescent Manor PO Box 2148 Oilton, New Jersey 07015 All rights of any nature 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, computer database entry, or networking, or in any manner whatsoever without written permission from the Publisher. Preface During the last 10 years, the role of specific nutrients in cancer prevention and cancer treatment has been the subject of intense basic, preclinical, and clinical research. At present, the major focus of nutri tional oncology is on the mechanisms of carcinogenesis and their modification by nutrients and on cancer prevention studies in animals and humans. Some human epidemiological studies have confirmed the hypothesis, developed on animals, that there is an inverse relation ship between the intake and/or level of !3-carotene, vitamin A vita min E, or vitamin C and the risk of cancer, whereas others have shown no such relationship. This is not unexpected, since the protective effect of individual nutrients may be too small to be detected by epidemiological methodologies in which a single vitamin or mineral is considered as one variable. Conclusive evidence regarding the role of nutrients in human cancer prevention will come from a well designed human intervention study using one or more nutrients in a population that has a high risk of developing cancer. The involvement of specific nutrients in the regulation of protooncogene expression has just begun. Also, some of the results of human intervention trials are beginning to yield interesting results. A large number of interna tional scientists from various disciplines, including cell biology, mo lecular biology, nutritional oncology, epidemiology, and public health, reviewed and discussed their most recent findings. The following topics were emphasized: 1. Mechanisms of carcinogenesis; 2. The mechanism of action of carotenoids, retinoids, vitamin E, pro tease inhibitors, and fatty acids; 3. Prevention of cancer in animals by carotenoids, retinoids, vitamin E, and selenium; 4. Nutritional causes of large-bowel cancer; v VI Preface 5. Preliminary results of intervention trials in China and Italy; and 6. The role of retinoids, vitamin D, and vitamins B6 and Bl in cancer treatment. This volume provides up-to-date information on basic and clini cal research in the area of nutritional oncology and will be useful to nutritionists, oncologists, cell biologists, pharmacologists, and epide miologists. The second meeting of the International Association for Vitamin and Nutritional Oncology (IA VNO) was sponsored by the Samuel Freeman Charitable Trust; National Cancer Institute; Henkel Corp oration; Cancer Research Institute; BASF Corporation; General Nu trition; Takeda, USA; Rhone-Poulene, Inc.; Hoffman-LaRoche, Inc.; Bristol-Myers Company; and American Cyanamid Company. Kedar N. Prasad Frank L. Meyskens, Jr. November 1989 Contents v Preface, K. N. Prasad and F. L. Meyskens, Jr. xi Nutrition and Cancer: An Overview of Present Reality and Future Goals, K. N. Prasad Mechanisms of Carcinogenesis 3 Two Operational Modes of Transmembrane Migration of Cyclic GMP Signal Pathway, R. K. Sharma Mechanisms of Action of Nutrients in Cancer Prevention 21 Counteractions of Retinoic Acid and Phorbol Ester Tumor Promoter Related to Changes in Protein Kinase Activities, W. B. Anderson, C. Liapi, J. Strasburger, R. Gopalakrishna, A. Plet, F. Raynaud, and D. Evain-Brion 39 Effect of Alpha Tocopheryl Succinate on Cell Differentiation and Adenylate Cyclase System, K. N. Prasad and J. Edwards-Prasad 53 Effect of Nutrition on Carcinogenesis: Mechanisms Involving Nitrosamines, C. S. Yang and S.-H. Lu 71 Mechanisms in Cancer Prevention by Dietary Antioxidants, C. Borek 79 Effects of Protease Inhibitors and Vitamin E in the Prevention of Cancer, A. R. Kennedy 99 Carotenoids Inhibit Chemically- and Physically-Induced Neoplastic Transformation During the Post-Initiation Phase of Carcinogenesis, J. S. Bertram, J. E. Rundhaug, andA.Pung vii viii Contents 113 Fatty Acids That Inhibit Cancer: Conjugated Dienoic Derivatives of Linoleic Acid, M. W. Pariza and Y. L. Ha 119 The Usefulness of In Vitro Assays and Animal Experiments in the Design of Chemopreventive Protocols with Beta-Carotene and Vitamin A on Tobacco Chewers, H. F. Stich, S. S. Tsang, B. Palcic, B. Mathew, R. Sankaranarayanan, and M. K. Nair 135 Dietary Modulation of Tobacco-Specific Carcinogen Activation, A. Castonguay, P. Pepin, M. A. Alaoui-Jamali, and G. Rossignol 155 Mechanisms of Specific Nutrients in the Prevention of Cancer, M. J. Hill Preclinical Studies in Cancer Prevention and Treatment 183 Reduction of Ultraviolet-Induced Immunosuppression and Enhanced Resistance to Ultraviolet-Induced Tumors by Retinyl Palmitate and Canthaxanthin, H. L. Gensler 197 Retinoids and Prevention of Experimental Cancer, R. C.Moon 207 Selenium and Vitamin E in Cancer Prevention, R. J. Shamberger 225 Vitamin B6 and Cancer, H. P. Fortmeyer Clinical Studies in Cancer Prevention and Treatment 241 The Nutritional Causes of Large-Bowel Cancer: Data from the Melbourne Colorectal Cancer Study and a 25-Year World Literature Overview, 1965-1989, G. Kune, S. Kune, B. Field, and L. Watson 261 An Intermediate Evaluation of the Nutrition Intervention Trials in Linxian, China, L. Jun-Yao 271 Vitamin D Analogs and the Treatment of Cancer, H. F.DeLuca 289 Control of Human Preneoplasia with Retinoids and Other Compounds, F. L. Meyskens, Jr. Contents ix 299 Carotenoids in Cancer Chemoprevention and Synergism with Retinol in Mastalgia Treatment, L. Santamaria, A. B. Santamaria, and M. dell'Orli 319 Adjuvant Immunotherapy of Breast Cancer: Prototypic Observations with Alpha-Tocopherol and Retinol, M. M. Black, R. E. Zachrau, and M. F. Katz 329 Vitamin B-6 and B-1 Status During Hormone Therapy of Gynecological Cancer, H. A. Ladner and R. M. Salkeld 339 Participants 341 Author Index 343 Subject Index Nutrition and Cancer An Overview of Present Reality and Future Goals Kedar N. Prasad President of IAV NO Introduction I welcome all of you to this second meeting of IA VNO. I am pleased to note that 14 countries have sent their delegations to at tend this conference. Since this is my last opportunity to address this distinguished audience as President of IAVNO, I decided to review some well known, some not so well known, and even some controver sial issues in order to generate new discussions on these matters. These decisions are deliberate, because I believe that our area of can cer research has an impact on the issue of public health and safety. Cancer Prevention In the USA, approx 900,000 new cases of cancer are detected ev ery year, and about 450,000 persons die of this disease each year. In the world, about 8 million new cases of cancer are diagnosed each year, and approx 5 million people die of this disease every year. Therefore, cancer has become one of the major health problems throughout the world. It is estimated that over 90% of the human cancers are caused by environmental, dietary, and life-style-related factors; approx 30% of these are attributed to tobacco smoking and about 40% to diet ary factors. From this estimation, it appears that over 70% of human xi