Table Of ContentNormal and Malignant Cell Growth
Recent Results in Cancer Research
Fortschritte der Krebsforschung
Progres dans les recherches sur Ie cancer
17
Edited by
V. G. Allfrey, New York· M. Allgower, Chur . K. H. Bauer, Heidelberg· 1. Beren
blum, Rehovoth . F. Bergel, London . J. Bernard, Paris . W. Bernhard, Villejuif
N. N. Blokhin, Moskva· H. E. Bock, Tubingen . P. Bucalossi, Milano· A. V. Chaklin,
Moskva . M. Chorazy, Gliwice . G. J. Cunningham, London . W. Dameshek, Boston
M. Dargent, Lyon . G. Della Porta, Milano . P. Denoix, Villejuif . R. Dulbecco, San
Diego· H. Eagle, New York· R. Eker, Oslo· P. Grabar, Paris· H. Hamperl, Bonn
R. J. C. Harris, London· E. Hecker, Heidelberg· R. Herbeuval, Nancy· J. Higgin
son, Lyon· W. C. Hueper, Bethesda· H. Isliker, Lausanne· D. A. Karnofsky, New
York· J. Kieler, K¢benhavn • G. Klein, Stockholm . H. Koprowski, Philadelphia
o.
L. G. Koss, New York· G. Martz, Zurich· G. Mathe, Villejuif . Muhlbock, Am
sterdam . G. T. Pack, New York· V. R. Potter, Madison· A. B. Sabin, Cincinnati
L. Sachs, Rehovoth . E. A. Saxen, Helsinki . W. Szybalski, Madison . H. T agnon,
Bruxelles . R. M. Taylor, Toronto . A. Tissieres, Geneve . E. Uehlinger, Zurich
R. W. Wissler, Chicago· T. Yoshida, Tokyo· L. A. Zilber, Moskva
Editor in chief
P. Rentchnick, Geneve
Springer-Verlag New York, Inc. 1969
Normal and Malignant
Cell Growth
Edited by
J.
R. M. Fry, M. L. Griem and W. H. Kirsten
With 85 Figures
Springer-Verlag New York, Inc. 1969
Symposium on Normal and Malignant Cell Growth
The University of Chicago School of Medicine
February 24th and 25th, 1968
Sponsored by the Swiss League agaimt Cancer
ISBN-l3: 978-3-642-48265-6 e-ISBN-13: 978-3-642-48263-2
DOl: 10.1007/978-3-642-48263-2
All righ ts reserved.
No part of this book may be translated or reproduced in any form
without written permission from Springer-Verlag.
© 1969 by Springer-Verlag New York Inc.
Softcover reprint of the hardcover 1s t edition 1969
Library of Congress Card Number 65-6383
Title No. 3632
Contents
Preface ix
Introduction xi
List of Participants Xlll
Normal Cell Kinetics
Chairman: M. FRY
General Introduction: L. LAMERTON . 1
Proliferative Capacity of Hemopoietic Stem Cells: L. LAJTHA 10
Discussion: Colony Forming Units in the Bone Marrow of
Partial Body Irradiated Mice: V. P. BOND and A. L. CARSTEN 21
Cellular Proliferation in the Liver: J. W. GRISHAM 28
Discussion: Cellular Proliferation in the Liver:
NANCY L. BUCHER, F. L. MOOLTEN and T. R. SCHROCK 43
Cell Proliferation in the Intestinal Epithelium: S. LESHER and J. BAUMAN 49
Discussion: Proliferation of Gastrointestinal Cells: M. LIPKIN 56
General Discussion 60
Normal Cell Kinetics (cont.)
Chairman: L. LAMERTON
Proliferation of Antibody Forming Cells: D. W. TALMADGE 66
Discussion: Proliferation of Antibody Forming Cells:
D. A. ROWLEY, F. W. FITCH and D. E. MOISER 75
Composition of Cell Life Cycle: D. M. PRESCOTT 79
Discussion: Methods and Criteria of Mammalian Cell Synchrony:
W. K. SINCLAIR . 90
Susceptibility of Intestinal Crypt Epithelium to Hydroxyurea and Other
Antitumor Agents: F. S. PHILIPS, S. S. STERNBERG and L. LENAZ 104
vii
viii CONTENTS
Discussion: Mammalian Cell Killing by Inhibitors of DNA Synthesis:
G. F. WHITMORE, J. BORSA, S. BACHETTI and F. GRAHAM . 109
Proliferation of Cancer Cells
Chairman: A. M. BRUES
General Introduction: The Growth of Tumor Cells under
Normal and Fasting Conditions: R. BASERGA and F. WIEBEL 118
Cell Proliferation during Carcinogenesis: A. B. REISKIN 128
Comparison Between the Rates of Proliferation of
Induced Malignancies and Their Normal Tissues of Origin:
F. D. BERTALANFFY . 136
The Use of Three-Dimensional Matrix Tissue Culture for Bioassay of Cancer:
A Progress Report: J. LEIGHTON, G. JUSTH and R. MARK . 147
Discussion: The Use of Three-Dimensional Matrix Tissue Culture
for Bioassay of Cancer: K. SANFORD . 163
Importance of the Non-Dividing Leukemia Cell:
A. M. MAUER, E. F. SAUNDERS and B. C. LAMPKIN 168
Discussion: Magnitude of Proliferating Fraction and Rate
of Proliferation of Populations of Leukemic Cells in Man:
B. D. CLARKSON, J. FRIED and M. OGAWA 175
Incorporation of Iodine-Labeled 5- Iodo-2'- Deoxyuridine
into DNA of Mouse Mammary Tumors: L. A. DETHLEFSEN 186
In Vivo Cell Kinetics of Human Cancers: M. TUBIANA 202
Summary: H. M. PATT . 218
Round-Table Discussion 226
Preface
This volume presents the Proceedings of the University of Chicago's third Cancer
Training Grant supported Teaching Symposium. This Symposium received much of
its support from grant number T12 CA 08077-02. Most of the planning of the
Symposium and most of the local editing of the Proceedings was carried out by Dr.
R. J. Michael Fry of the A.E.C. Argonne National Laboratory and by two members
of the Advisory Committee of the Cancer Training Grant, Drs. Melvin Griem and
Werner Kirsten. They carried the main responsibility for the Symposium.
The subject of the Symposium, "Normal and Malignant Cell Growth," was chosen
because, as the Proceedings reflect, it is a rapidly advancing field of endeavor which
is of utmost importance to the understanding of the processes of malignant neoplasia.
In fact, there is increasing evidence that knowledge of the kinetics of the cancer cell
will greatly influence approaches to cancer therapy.
Like the first two of these Teaching Symposia held in 1964 and 1966, this one
attracted about 400 students and staff from this medical institution as well as from
other medical centers in the Chicago area. The effective interplay of an excellent
group of scientists with a lively and responsive audience was evident as they considered
together a topic of great current interest in the field of neoplasia. Much of the credit
for the smooth organization and implementation of the Symposium must go to Mrs.
Brenda K. Pickens who was ably assisted by Mrs. Jean B. Newgard. Mrs. Pickens'
contribution to recording, transcribing and editing the Proceedings is also gratefully
acknow ledged.
As director of the Cancer Training Grant, I also want to express my appreciation
for the contributions of the Advisory Committee to this program and specifically to
the success of this Symposium. They are as follows:
GEORGE E. BLOCK, Professor of Surgery and Coordinator of Education in Clinical
Oncology.
MELVIN L. GRIEM, Associate Professor of Radiology in the A.E.C. Argonne Cancer
Research Hospital and Director, Registry of Neoplastic Diseases.
ELWOOD V. JENSEN, American Cancer Society-Charles Hayden Foundation Research
Professor of Physiology in the Ben May Laboratory for Cancer Research.
JOSEPH B. KIRSNER, Professor of Medicine and Chief of Gastroenterology.
WERNER H. KIRSTEN, Professor of Pathology and Pediatrics and N.C.I. Career De
velopment Awardee.
JOHN V. PROHASKA, Professor of Surgery.
HENRY RAPPAPORT, Professor of Pathology and Director of Surgical Pathology.
ROBERT W. WISSLER, Ph.D., M.D.,
Director of Cancer Training Grant
Professor and Chairman
Department of Pathology
University of Chicago
Pritzker School of Medicine and
in the A.E.C. Argonne Cancer Research
Hospital
Introduction
The understanding of the proliferation of cells and tissues has proceeded at a rapid
pace over the last decade. The one particularly significant accomplishment has been
the introduction of labelled DNA precursors and the use of high resolution auto
radiography. These techniques have allowed the physiologist and the pathologist to
examine many additional parameters in the process of cell proliferation both in vitro
and in vivo. Knowledge of cell proliferation may be useful in improving our methods
of treatment of a number of diseases and particularly a number of the human cancers
which defy current treatment methods.
The Cancer Training Grant Director at The University of Chicago, with the
help of his Advisory Committee, made plans to hold a teaching symposium on the
subject of normal and malignant cell growth as part of the annual program of train
ing in oncology at The University of Chicago. The objectives of the conference were
to survey the recent accomplishments in this field and to present for the medical
students and house staff the newer developments in the cell proliferation kinetics of
normal tissues. As with the previous symposia sponsored by this training grant, lead
ing scientists in various aspects of cell proliferation were invited to present general
reviews as well as their latest results. In a number of instances the speaker was fol
lowed by an invited discussant.
The first day of the symposium, February 24, 1968, was devoted to the under
standing of cell proliferation kinetics and was devoted to the general topics related
to normal cell proliferation. A discussion followed this first day symposium so that
the main speakers could exchange additional information and could answer questions
from the audience. This discussion was especially stimulating under the leadership of
Dr. Hewson Swift. On February 25, 1968, the participants considered our current
knowledge of the proliferation of tumors. The symposium was summarized most ably
by Dr. Harvey Patt.
The form of abbreviation for tritiated thymidine still shows the individuality of
authors, but as their meaning is clear, no changes have been made. In order to prevent
further reduction of figures, some have been placed to make optimal use of page size.
It is felt that the reader will use the table of contents for his guidance and we hope
therefore will not miss the presence of an index.
This symposium held at The University of Chicago has stimulated a number of
the staff and the graduate and undergraduate students to organize a weekly confer
ence devoted to the discussion of problems related to cell kinetics.
The symposium was supported in part by the Rosa Kuhn Levy Fund, The Chicago
Tumor Institute, the Rockefeller Foundation Grant for the Activities in Nuclear
Medicine (Pharmacology), and mainly by the Cancer Training Grant of the National
Cancer Institute #T12 CA 08077-02.
Weare grateful to all who have made this conference possible.
R. J. M. FRY, M. 1. GRIEM, and W. H. KIRSTEN
List of Participants
BASERGA, RENATO GRISHAM, J. W.
Fels Research Institute and Department of Pathology
Department of Pathology Washington University
Temple University St. Louis, Missouri
Philadelphia, Pennsylvania
LAJTHA, LASZLO G.
BERTALANFFY, FELIX D. Patterson Research Laboratories
Department of Anatomy
Christie Hospital and Holt Radium
University of Manitoba
Institute
Winnipeg, Canada
Manchester, England
BOND, VICTOR P.
LAMERTON, LEONARD F.
Medical Department
Department of Biophysics
Brookhaven National Laboratory
Institute of Cancer Research
Upton, New York
Surrey, England
BRUES, AUSTIN M.
Division of Biological and LEIGHTON, JOSEPH
Medical Research Department of Pathology
Argonne National Laboratory and University of Pittsburgh
The University of Chicago Pittsburgh, Pennsylvania
Argonne, Illinois
LESHER, SAMUEL W.
BUCHER, NANCY L. R. Department of Radiology
John Collings Warren Laboratories Allegheny General Hospital
Huntington Memorial Hospital Pittsburgh, Pennsylvania
Harvard University
Boston, Massachusetts LIPKIN, MARTIN
Department of Medicine
CLARKSON, BAYARD
Cornell University
Sloan-Kettering Institute for
New York, New York
Cancer Research
New York, New York MAUER, ALVIN M.
Children's Hospital Research
DETHLEFSEN, LYLE A.
Foundation and
Department of Radiology
Department of Pediatrics
University of Pennsylvania
University of Cincinnati
Philadelphia, Pennsylvania
Cincinnati, Ohio
J.
FRY, R. MICHAEL
Division of Biological and PATT, HARVEY M.
Medical Research Laboratory of Radiobiology
Argonne National Laboratory University of California
Argonne, Illinois San Francisco, California
xiii
xiv LIST OF PARTICIPANTS
PHILIPS, FREDERICK S. SINCLAIR, WARREN K.
Pharmacology Division Division of Biological and
Sloan-Kettering Institute Medical Research
for Cancer Research Argonne National Laboratory
New York, New York Argonne, Illinois
PRESCOTT, DAVID
SWIFT, HEWSON H.
Institute for Developmental Biology
Department of Biology
University of Colorado
University of Chicago
Boulder, Colorado
Chicago, Illinois
REISKIN, ALLAN B.
Division of Biological and Medical TALMAGE, DAVID W.
Research Departments of Microbiology and
Argonne National Laboratory and Medicine
The University of Chicago University of Colorado
Argonne, Illinois Denver, Colorado
ROWLEY, DONALD A.
TUBIANA, MAURICE
Department of Pathology
Department of Radiation
University of Chicago
Institute Gustave-Roussy
Chicago, Illinois
Villejuif, France
SANFORD, KATHERINE K.
Laboratory of Biology WHITMORE, GORDON
National Cancer Institute University of Toronto and
National Institutes of Health Ontario Cancer Institute
Bethesda, Maryland Toronto, Canada
