Table Of ContentNutrients 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
