Table Of ContentMECHANISMS OF CARCINOGENESIS
Cancer Growth and Progression
SERIES EDITOR: HANS E. KAISER
Department of Pathology, University of Maryland, Baltimore, Md, U.S.A.
Scientific Advisors:
Kenneth W. Brunson / Harvey A. Gilbert / Ronald H. Goldfarb / Alfred L. Goldson / Elizier Gorelik /
Anton Gregl / Ronald B. Herberman / James F. Holland / Ernst H. Krokowski t / Arthur S. Levine /
Annabel G. Liebelt / Lance A. Liotta / Seoras D. Morrison / Takao Ohnuma / Richard L. Schilsky /
Harold L. Stewart / Jerome A. Urban / Elizabeth K. Weisburger / Paul V. Woolley
Volume 1: Fundamental Aspects of Cancer
Volume Editor: Ronald H. Goldfarb
ISBN 0-89838-990-9
Volume 2: Mechanisms of Carcinogenesis
Volume Editor: Elizabeth K. Weisburger
ISBN 0-89838-991-7
Volume 3: Influence of Tumor Development on the Host
Volume Editor: Lance A. Liotta
ISBN 0-89838-992-5
Volume 4: Influence of the Host on Tumor Development
Volume Editor: Ronald B. Herberman
ISBN 0-89838-993-3
Volume 5: Comparative Aspects of Tumor Development
Volume Editor: Hans E. Kaiser
ISBN 0-89838-994-1
Volume 6: Etiology of Cancer in Man
Volume Editor: Arthur S. Levine
ISBN 0-89838-995-X
Volume 7: Local Invasion and Spread of Cancer
Volume Editor: Kenneth W. Brunson
ISBN 0-89838-996-8
Volume 8: Metastasis / Dissemination
Volume Editor: Elizier L. Gorelik
ISBN 0-89838-997-6
Volume 9: Cancer Management in Man: Detection, Diagnosis, Surgery, Radiology, Chronobiology,
Endocrine Therapy
Volume Editor: Alfred L. Goldson
ISBN 0-89838-998-4
Volume 10: Cancer Management in Man: Biological Response Modifiers, Chemotherapy, Antibiotics,
Hyperthermia, Supporting Measures
Volume Editor: Paul V. Woolley
ISBN 0-89838-999-2
Complete set: ISBN 0-89838-989-5
Mechanisms of
Carcinogenesis
Edited by
ELIZABETH K. WEISBURGER
National Cancer Institute, National Institutes of Health,
Bethesda, Md., U.S.A.
Kluwer Academic Publishers
DORDRECHT / BOSTON / LONDON
Library of Congress Cataloging in Publication Data
Mechanisms of carcinogenesis.
(Cancer growth and progression; v. 2)
Includes index.
1. Carcinogenesis. I. Weisburger, Elizabeth K.
II. Series. [DNLM: 1. Carcinogens. 2. Carcinogens,
Environmental. 3. Neoplasms--etiology.
QZ 200 C2151518 v.2]
RC268.5.M425 1988 616.99'4071 87-24664
ISBN-13: 978-94-010-7641-8 e-ISBN-13: 978-94-009-2526-7
DOl: 10.1 007/978-94-009-2526-7
Published by Kluwer Academic Publishers,
P.O. Box 17, 3300 AA Dordrecht, The Netherlands.
Kluwer Academic Publishers incorporates
the publishing programmes of
Martinus Nijhoff, Dr W. Junk, D. Reidel, and MTP Press.
Sold and distributed in the U.S.A. and Canada
by Kluwer Academic Publishers,
101 Philip Drive, Norwell, MA 02061, U.S.A.
In all other countries, sold and distributed
by Kluwer Academic Publishers Group,
P.O. Box 322, 3300 AH Dordrecht, The Netherlands.
Cover design by Jos Vrolijk.
All rights reserved
© 1989 by Kluwer Academic Publishers
Softcover reprint of the hardcover 1s t edition 1989
No part of the material protected by this copyright notice may be reproduced or utilized in any form
or by any means, electronic or mechanical, including photocopying, recording, or by any information
storage and retrieval system, without written permission from the copyright owners.
TABLE OF CONTENTS
Introduction . . . . . . . . . . . . . . . . . . . . . . VII
List of contributors . . . . . . . . . . . . . . . . . . . IX
1. The influence of human behavior on neoplastic progression
H.E. KAISER ................ .
2. The influence of stressors on the progression of neoplastic change
H. ANISMAN, J. IRWIN and L.S. SKLAR ...... . 7
3. The seven types of causes of neoplastic growth - an organismic view
H.E. KAISER . . . . . . . . . . . . . . . . . . . . . . 19
4. Chemoprevention research
W.F. MALONE . . 31
5. Premalignant and non-invasive lesions of the urinary bladder
S.L. JOHANSSON and S.M. COHEN. . . . . . . 43
6. Species-specific aspects of the carcinogenicity of chloroform
E.K. WEISBURGER . . . . . . . . . . . . . . 51
7. Carcinogenic effects of ionizing radiation
A.c. UPTON ........ . 54
8. Selected aspects of viral carcinogenesis
P.S. SARIN ........ . 71
9. The quantum theory of carcinogenesis - a short review
J. LADIK and P. OTTO .......... . 84
10. Cellular oncogene activation by chromosomal translocation
K.R. HAREWOOD. . . . . . . . . . . . . . . 87
11. Amplification of the oncogene N-Myc as a correlate to advanced stage in human neuroblastomas
M. SCHWAB .................................. . 92
12. Potential roles of activated proto-oncogenes in malignant progression
G.E. GALLICK . . . . . . . . . . . . . . . . . . . . 98
13. Oncogenes and their encoded products as targets for cancer therapy
D.L. SLATE ..................... . 106
14. Methods to study RAS oncogene-mediated induction of the metastatic phenotype
UP. THORGEIRSSON, T. TURPEENNIEMI-HUJANEN, M. BALLIN and L.A. LIOTTA. 113
15. Oncogene products as potential therapeutic targets for control of established metastatic disease
R.H. GOLDFARB and K.W. BRUNSON . . . . . . . . . . . . . . . . . . . . . . . 119
16. Neoplastic cell stages and progression in experimental hepatocarcinogenesis
E. SCHERER ....................... . 128
17. Characterization of eleven important transplantable murine tumors from the standpoint of morphology,
pyrimidine biosynthesis and responsiveness to pyrimidine antimetabolites
T.W. KENSLER, H.M. SCHULLER, H.N. JAYARAM and D.A. COONEY. . . . . . . . . .. 145
18. Use of organ explant and cell culture in cancer research
J.H. RESAU and J.R. COTTRELL . . . . . . . . . . . . . . . . . . . 157
v
VI Contents
19. Season of operation and differential long-term progression: clinical, statistical, and psychological issues
E.H. KROKOWSKI, H.w. WENDT and P.A. HOMYAK. . . . . . . . . . . . . 160
20. Endogenous factors affecting the progression of carcinogen-induced rat mammary carcinomas
C.W. WELSCH. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
21. Age factors in the presence of selected neoplasms
H.E. KAISER . . . . . . . . . . . . . 179
22. Extremely low frequency electromagnetic fields as possible promotors of carcinogenesis
N. WERTHEIMER .......................... . 188
23. Medical geography and neoplasms
J.P. FULTON .... . 191
Index of subjects ........ . 194
INTRODUCTION
Human behavior, including stress and other factors, plays but also the possibility of intervention in specific stages. In
an important role in neoplasia, although too little is known addition, variables which affect cancer development as well
on the reasons for such development. Carcinogens, which as some endogenous factors can be better delineated
help initiate the neoplastic process, may be either synthetic through such investigations.
or naturally-occurring. Cancer causation may be ascribed to The topics of this volume encompass premalignant non
certain chemicals, physical agents, radioactive materials, invasive lesions, species-specific aspects of carcinogenicity,
viruses, parasites, the genetic make-up of the organism, and radiation, viruses, a quantum theory of carinogenesis, onco
bacteria. Humans, eumetazoan animals and vascular plants genes, and selected environmental carcinogens.
are susceptible to the first six groups of cancer causes, whe
reas the last group, bacteria, seems to affect only vascular
plants. Neoplastic development may begin with impairment
ofJmdy defenses by a toxic material (carcinogen) which acts
as an initiator, followed by promotion and progression to an
overt neoplastic state. Investigation of these processes Series Editor Volume Editor
allows not only a better insight into the mechanism of action Hans E. Kaiser Elizabeth K. Weisburger
vii
ACKNOWLEDGEMENT
Inspiration and encouragement for this wide ranging project on cancer distribution and dissemination from a comparative
biological and clinical point of view, was given by my late friend E. H. Krokowski.
Those engaged on the project included 252 scientists, listed as contributors, volume editors and scientific advisors, and a
dedicated staff. Special assistence was furnished by J. P. Dickson, J. A. Feulner, and I. Theloe.
1. Bauer, D. L. Fisher, S. Fleishman, K. Joshi, A. M. Lewis, J. Taylor and K. E. Yinug have provided additional assistence.
The firm support of the publisher, especially B. F. Commandeur, is deeply appreciated. The support of the University of
Maryland throughout the preparation of the series is acknowledged.
To the completion of this undertaking my wife, Charlotte Kaiser, has devoted her unslagging energy and invaluable support.
CONTRIBUTORS
Hymnie ANISMAN, Ph.D. Gary E. GALLICK, Ph.D.
Department of Psychology Department of Tumor Biology
Carleton University Virology Section
Ottawa, Ontario, KLS 5B6 Box 79
Canada University of Texas
M.D. Anderson Hospital and Tumor Institute
Marina BALLIN, PhD. 6723 Bertner Ave.
Laboratory of Pathology Houston
National Cancer Institute/ Texas 77030, USA
National Institutes of Health
Bethesda Ronald H. GOLDFARB, Ph.D.
Maryland 20892, USA Pittsburgh Cancer Institute
230 Lothrop St.
K.W. BRUNSON, Ph.D. Pittsburgh
Department of Immunology & Pennsylvania 15213-2592
Infectious Diseases USA and Department of Pathology
Pfizer Central Research University of Pittsburg
Eastern Point Road School of Medicine
Croton
Connecticut 06340, USA K.R. HAREWOOD, Ph.D.
Department of Immunology and
Samuel M. COHEN, M.D., Ph.D. Infectious Diseases
Department of Pathology and Microbiology Pfizer Central Research
University of Nebraska Eastern Point Road
Medical Center Croton
42nd and Dewey Avenue Connecticut 06340, USA
Omaha
Nebraska 68105, USA P.A. HOMYA K, MHA
Department of Psychology
David A. COONEY, MD. MacAlester College
Laboratory of Medicinal Chemistry and Pharmacology 1600 Grand Ave.
National Cancer Institute/ St. Paul
National Institutes of Bethesda Minnesota 55105, USA
Maryland 20892, USA
J. IRWIN, Ph.D.
J.R. COTTRELL, M.S.
Department of Psychology
Department of Pathology
Queens University
School of Medicine
Kingston, Ontario K7L3N6
University of Maryland
Canada
10 S. Pine Street
Baltimore
Maryland 21201, USA Hiremagalur N. JAY ARAM
Division of Cancer Treatment
John P. FULTON, Ph.D. National Institutes of Health
Rhode Island Cancer Registry Bethesda
Rhode Island Department of Health Maryland 20892, USA
Office of Health Statistics
Cannon Building - 75 Davis Street Sonny L. JOHANSSON, M.D., Ph.D.
Providence, RI 02908-509 Department of Pathology and Microbiology
and Department of Community Health University of Nebraska Medical Center
Brown University 42nd and Dewey Avenue
Providence Omaha
Rhode Island 02902, USA Nebraska 68105, USA
ix
