Advances in Cancer Research [Vol II]

543 Pages·1954·29.603 MB·English

by  J. Greenstein, et al.,

ADVANCES IN CANCER RESEARCH
Volume I1
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ADVANCES IN
CANCER RESEARCH
EDITED BY
JESSE P. GREENSTEIN
National Cancer Institute, US.P ublic Health Service,
Bethesda, Maryland
ALEXANDER HADDOW
Chester Beatty Research Institute, Royal
Cancer Hospital, London, England
Volume I I
ACADEMIC PRESS INC., PUBLISHERS
NEW YORK, N.Y.
1954
COPYRIGHT 1954, BY
ACADEMIC PRESS INC.
125 East 23rd Street, New York 10, N.Y.
All Rights Reserved
No part of this book may be reproduced in any form, by photostat,
microfilm, or any other means, without written permission from
the publishers.
Library of Congress Catalog Card Number: 52-13360
PHINTED IN THE UNITED STATES OF AMERICA
CONTRIBUTORS TO VOLUME II
PETER ALEXANDERC,h ester Beatty Research Institute, Royal Cancer
Hospital, London, and Chemistry Department, Imperial College,
London, England
G. M. BADaER, Chemistry Department, University of Adelaide, Australia
JEANNE C. BATEMANW, arwick Memorial Clinic, George Washington
University Medical School, Washington, D.C.
I. BERENBLUMDe, partment of Experimental Biology, The Weizmann
Institute of Science, Rehovoth, Israel
AUSTINM . BRUESD, ivision of Biological and Medical Research, Argonne
National Laboratory, Lemont, Illinois
.JAMES CRAIGIEIm, perial Cancer Research Fund, London, England
LEONARDD. FENNINQERNa, tional Cancer Institute, National Institutes
of Health, Bethesda, Maryland
M. GU~CRIINns,t itut de Recherches sur le Cancer, Vzllejuif (Seine), France
CALVINT . KLOPP,W arwick Memorial Clinic, George Washington Uni-
versity Medical School, Washington, D.C.
I,. W. LAW, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland
G. BURROUQHMSI DER,N ational Cancer Institute, National Institutes of
Health, Bethesda, Maryland
C. OBERLINQI,n stitut de Recherches sur le Cancer, VilZejuif (Seine), F rance
C. CHESTERS TOCK,D ivision of Experimental Chemotherapy, Sloan-
Kettering Institute for Cancer Research, New York
V
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PREFACE
In the year which has elapsed since the publication of Volume I of
Advances in Cancer Research, the editors have been gratified by the favor-
able reception accorded to it, equally by their fellow workers and by the
scientific press. This they regard not only as a general encouragement of
the new enterprise but also as a reflection of the value, certainly no less
in this than in any other scientific field, of the authoritative review. Since
their aim is not only to consolidate the venture but, so far as is possible,
to improve it, they take the present opportunity of welcoming sugges-
tions to this end, whether concerned with particular topics or aspects
which most merit inclusion, or with policy as a whole.
In the current volume, the central theme of carcinogenesis again finds
a prominent place, as, for example, in the review of carcinogenesis and
tumor pathogenesis by Dr. I. Berenblum, whose own work has elucidated
so many of the factors involved; and in that of Dr. G. M. Badger, who,
not only as a pupil of Professor J. W. Cook at the Royal Cancer Hospital
in London and at the University of Glasgow, but also by virtue of his
own contributions subsequently, is especially qualified to deal with the
relationships of chemical constitution and carcinogenic activity. Although
the list of chemical carcinogens is doubtless still incomplete, and much
may still be learned from the chemical interrelationships of those already
known, within the past few years a new emphasis has inevitably been
given to problems of their mode of action, involving a shift of interest
toward those macromolecular receptors with which, it would appear, they
most probably combine. This development has been greatly stimulated
by the discovery of carcinogenic activity in a whole range of “biological
alkylating agents,’’ the reactions of which, among other carcinogens, are
dealt with in a contribution by Dr. P. Alexander. So far at least as their
biological end-results are concerned, many of these alkylating agents may
very reasonably be described as “radiomimetic,” lending special signifi-
cance to the facts, first that the earliest experimentally induced tumors
owed their origin to ionizing radiations, and, second, that the total of
carcinogenic agents has been greatly increased, through the wealth of
radioisotopes accruing from the atomic energy programs of the past ten
years; these, and their practical bearings, are considered in a contribution
by Dr. A. M. Brues.
From its beginnings, research into the etiology of cancer has been
vii
viii PREFACE
enlivened by the controversy between those who subscribe to the impor-
tance of a process of infection-especially by viral agents-and those
others who believe the reverse. Even though many must judge the anti-
thesis to be a false one, the issue in reality is still undecided; contributions
which throw light upon it include a vigorous review by Dr. C. Oberling
and Dr. M. Guerin, a survey of genetic studies by Dr. L. W. Law, and an
account, by Dr. J. Craigie, of the survival and preservation of tumors
in the frozen state-the last including details not merely of great theoreti-
cal interest but of much practical value as well.
Apart altogether from etiology and pathogenesis, increased note has
been paid of recent years to the systemic and nutritional consequences of
tumor growth once established, and the review by Dr. L. D. Fenninger
and Dr. G. Burroughs Mider, on energy and nitrogen metabolism, is of
special interest for its relevance to the disease in man. The same applies
in marked degree to the contribution of Dr. C. Chester Stock on experi-
mental cancer chemotherapy, and that of Dr. C. T. Klopp and Dr.
Jeanne C. Bateman on the clinical use of the nitrogen mustards. Admitted
that the chemotherapeutic agents of the future are likely to be very
different in their nature, specificity, and potency from those at present
used, it is a matter of no little consequence that limited gains continue
to be recorded, and that the harvest of benefit grows, even if slowly, from
year to year.
It is our ambition, and hope, that these volumes may serve not merely
as an annual chronicle of progress, but as a recurring stimulus to the
work ahead.
THEE DITORS
February, i 954
CONTENTS
CONTRIBUTORS TO VOLUME 11 . . . . . . . . . . . . . . . . . . . . . . . V
PREFAC.~. . . . . . . . . . . . . . . . . . . . . . . . . . . . vil
The Reactions of Carcinogens with Macromolecules
BY PETERA LEXANDERC,h ester Beatty Research Institute. Royal Cancer Hospital.
London. and Chemistry Departmentl Imperial College. London. England
.
I Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
I1 . Biological Alkylating Agents . . . . . . . . . . . . . . . . . . . . 4
I11. Ionizing Radiations . . . . . . . . . . . . . . . . . . . . . . . . 42
IV. Polycyclic Hydrocarbons . . . . . . . . . . . . . . . . . . . . . . 5 5
V . Compounde Containing Amino Groups . . . . . . . . . . . . . . . . 62
VI. Carcinogenic Polymers . . . . . . . . . . . . . . . . . . . . . . . 65
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
Chemical Constitution and Carcinogenic Activity
. .
BY G M BADQERC. hemistry Department. University of Adelaide. Australia
.
I Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
I1. Historical . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
.
I11 Polycyclic Aromatic Hydrocarbons . . . . . . . . . . . . . . . . . . 80
.
IV Aeo Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . 112
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
Carcinogenesis and Tumor Pathogenesis
.
BY I BERENBLUDMe~pa rtment of Experimental Biology. The Weizmann Institute of
Science, Rehovoth. Israel
.
I Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 129
.
I1 Nature of Response to Carcinogenic Action . . . . . . . . . . . . . 1 30
.
I11 Genetic Factors Influencing Carcinogenesis. . . . . . . . . . . . . . 1 39
.
IV Influence of Age. Sex. and Hormonal Factors . . . . . . . . . . . . . 1 42
.
V Dietary Factors Influencing Carcinogenesis. . . . . . . . . . . . . . .1 44
.
VI Effect of Solvents on Carcinogenesis. . . . . . . . . . . . . . . . . 1 47
VII. Irritation and Carcinogenesis. . . . . . . . . . . . . . . . . . . . 151
.
VIII Initiating and Promoting Action as Independent Stages of Carcinogenesis 155
.
IX Histogenesis of Preneoplasia . . . . . . . . . . . . . . . . . . . . 159
.
X General Discussion . . . . . . . . . . . . . . . . . . . . . . . . 163
Referencee . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164
Ionizing Radiations and Cancer
.
BY AUSTIN M BRUES.D ivision of Biological and Medical Research. Argonne National
Laboratory, Lemont. Illinois
.
I Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
.
I1 Basis of Radiation Effects . . . . . . . . . . . . . . . . . . . . 1 78
.
I11 Radiation Carcinogenesis. . . . . . . . . . . . . . . . . . . . . 179
.
IV Mechanism of Carcinogenesis. . . . . . . . . . . . . . . . . . . . 182
.
V The Mutation Hypothesis . . . . . . . . . . . . . . . . . . . . . 184
ix