Table Of ContentProstaglandin and
Lipid Metabolism in
Radiation Injury
Prostaglandin and
Lipid Metabolism in
Radiation Injury
Edited by
Thomas L. Walden, Jr.
and
Haywood N. Hughes
Armed Forces Radiobiology Research Institute
Bethesda, Maryland
Plenum Press • New York and London
Library of Congress Cataloging in Publication Data
International Conference on Prostaglandins and Lipid Metabolism in Radiation Injury
(1986: Rockville, Md.)
Prostaglandin and lipid metabolism in radiation injury 1 edited by Thomas L.
Walden, Jr. and Haywood N. Hughes.
p. cm.
"Proceedings of the International Conference on Prostaglandins and Lipid
Metabolism in Radiation Injury, held October 2-3, 1986, in Rockville, Maryland"
T.p. verso.
Includes bibliographies and index.
1. Radiation-Physiological effect-Congresses. 2. Radiation injuries-Congresses.
3. Prostaglandins-Effect of radiation on-Congresses. 4. Lipids-Effect of radiation
on-Congresses. 5. Radiation-protective agents-Congresses. I. Walden, Thomas L.
II. Hughes, Haywood N. III. Title. [DNLM: 1. Lipids-metabolism-congresses. 2.
Prostaglandins-metabolism -congresses. 3. Radiation Injuries-congresses. WN
610 163p 1986)
QP82.2.R3157 1986 87-32663
616.98'9707-dc19 CIP
ISBN-13 :978-1-4684-5459-8 e-ISBN-13:978-1-4684-5457-4
DOl: 10.1007/978-1-4684-5457-4
Proceedings of the International Conference on Prostaglandins and Lipid
Metabolism in Radiation Injury, held October 2-3, 1986, in Rockville, Maryland
© 1987 Plenum Press, New York
Softcover reprint of the hardcover 1st edition 1987
A Division of Plenum Publishing Corporation
233 Spring Street, New York, N.Y. 10013
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted
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PREFACE
This volume contains the proceedings of the International Conference on
Prostaglandins and Lipid Metabolism in Radiation Injury held in Rockville,
Maryland, on October 2-3, 1986. Over 200 persons from eight countries attended
the program, which consisted of 24 oral presentations and 38 poster presentations.
Forty-two of those presentations have been included in this volume. The conference
was sponsored by the Armed Forces Radiobiology Research Institute, located in
Bethesda, Maryland.
The effects of radiation on lipid synthesis and membrane damage are aptly
summarized in the first five chapters. These chapters describe the effects of radiation
on lipid peroxidation of model membranes, and the role of lipid composition in
mammalian cell death and in bacterial radio- and thermosensitivity. In bacteria,
lipid peroxidation is not essential for radiation-induced cell death.
One of the key points of the conference was the paradoxical nature of the
radiobiology of eicosanoids. On the one hand, eicosanoids are mediators of damage;
on the other, they are radioprotective agents. It is clear from the literature and
from the data presented at the conference that both of these properties may also
be observed as a consequence of radiotherapy. Some studies indicate that
nonsteroidal anti-inflammatory drugs may minimize or prevent certain radiation
induced damage, but other studies show no positive effect. It was pointed out at
the conference that care should be exercised in manipulating the eicosanoid response
of tumors to favor radiotherapy because in blocking either the cyclooxygenase
pathway or the lipoxygenase pathway, arachidonic acid may be shunted through
the other pathway and elicit similar radiation-induced damage or tumor protection.
Two additional chapters are devoted to prostaglandins and cancer, showing the
potential uses of nonsteroidal anti-inflammatory drugs in therapy and also
demonstrating that prostaglandins are radioprotective to tumor cells. Both the
prostaglandins and the leukotrienes have been shown to exhibit radioprotective
qualities. In addition, the latest information has been included on the alteration
of prostaglandin levels in humans following total-body irradiation for bone marrow
transplants. The increase in urinary 6-keto PGF1a has now been observed in humans
and in laboratory animals postirradiation.
The conference highlighted a number of methods for the detection and quantitation
of lipid peroxidation and eicosanoids. The proceedings is organized to reflect the
methods of detecting eicosanoids and lipid peroxidation, and summarizes the state
of the art in those fields. The definitive detection is represented by the extreme
v
vi Preface
sensitivity and characteristic spectral analysis of the GC-mass spectrometer, with
which femtogram quantities can be detected. The rapidly developing field of enzyme
labeled immunoassay (ELISA) is summarized, including the detection of eicosanoids
using acetylcholine esterase. This technique permits the detection of eicosanoids
down to one picogram per well and does not require the use of radiolabeled
compounds. A relatively new technique for the introduction of nonvolatile samples
for mass spectroscopic analysis is the thermospray interface. As new techniques
and lower limits of sensitivity have been acquired, the list of eicosanoid metabolites
and their biological properties that have been identified will most certainly grow.
The picture becomes more complicated in accounting for the metabolites, the
distributions, and their contributions to either radiation injury or radioprotection.
The effects of ionizing and nonionizing radiations on eicosanoid and lipid
metabolism are presented on experimental systems ranging from liposomes and
bacteria to man. Very little work has been done with either the platelet-activating
factor or leukotrienes regarding their roles in radiation injury. Reports in this volume
demonstrate that the production of both compounds is increased in response to
radiation exposure. The conference has summarized much of the complexity within
the field and pointed out the need for more research and, perhaps, the need for
a future conference.
The editors gratefully acknowledge the support and assistance of Junith A. Van
Deusen, Janet B. Gillette, Beth A. Roberts, Modeste E. Greenville, and Nancy
F. Brown in producing this volume. We also thank Beverly S. Geisbert, Sonia
Jones, Carolyn B. Wooden, and Sandra L. Work for preparing the manuscripts.
Thomas L. Walden, Jr.
Haywood N. Hughes
Editors
The articles in this volume have been accepted by a peer review process. The editors
express their sincere appreciation to the following members of the Editorial Board:
Birandra Bsinha, Bethesda, MD
William Blakely, Bethesda, MD
William Cramp, London, England
John Delaney, Minneapolis, MN
Mildred Donlon, Bethesda, MD
Elizabeth Duell, Ann Harbor, MI
Amiram Eldor, Jerusalem, Israel
Thomas Eling, Research Triangle Park, NC
Tony Fitz, Bethesda, MD
Frank Fitzpatrick, Kalamazoo, MI
Aaron Friedman, Madison, WI
Elaine Gallin, Bethesda, MD
Charles Geard, New York, NY
Kenneth Honn, Detroit, MI
Sree Kumar, Bethesda, MD
Edwardo Lapetina, Research Triangle Park, NC
Shirley Lehnert, Montreal, Canada
Paul Marques, Tucson, AZ
David McClain, Bethesda, MD
James McGee, Kalamazoo, MI
Douglas Morton, Kalamazoo, MI
Robert Murphy, Denver, CO
Ruth Neta, Bethesda, MD
Myra Patchen, Bethesda, MD
Lawrence Patterson, Notre Dame, ID
John Redpath, Irvine, CA
Myron Peterson, Boston, MA
Edappallath Radha, Bethesda, MD
J ames Raleigh, Edmonton, Alberta, Canada
David Rubin, Chicago, IL
John Sauk, Baltimore, MD
Linda Steel, Bethesda, MD
Mary Stuart, Syracuse, NY
Yashesh Vaishnav, Bethesda, MD
Jack Vanderhoek, Washington, DC
Robert Wainberg, Madison, WI
William Ward, Chicago, IL
Joseph Weiss, Bethesda, MD
Michael Wynalda, Kalamazoo, MI
vii
CONTENTS
RADIATION EFFECTS ON LIPID SYNTHESIS
AND MEMBRANE DAMAGE
Radiation Peroxidation in Model Membranes 3
J. A. Raleigh
Role of Membrane Lipid Composition in Radiation-Induced Death of
Mammalian Cells 29
A. W. T. Konings
Influence of Membrane Lipid Composition and Organization on Radio
and Thermosensitivity of Bacteria 45
M. B. Yatvin, O. Yukawa, and W. H. Dennis
Role of Membranes, Free Radicals, and Copper in Radiation-Induced
Changes in Quaternary Structure of DNA: Some Clinical
Implications 59
W. A. Cramp, A. M. George, J. C. Edwards, S. A. Sabovljev,
G. Harris, L. E. Hart, H. Lambert, and M. B. Yatvin
Role of Lipid Peroxidation in Radiation Damage and Repair of Cell
Membranes in the Thermophilic Bacterium Thermus thermophilus 73
S. Suzuki
Macromolecule Effects on Prostacyclin Production and Measurement 79
R. M. Price, D. M. Gersten, and P. W. Ramwell
Inositol Lipid Turnover, Ca2+ Mobilization, and Increased Ca2+ Influx in
Heat-Stressed Cells 85
M. A. Stevenson, E. K. Farnum, G. M. Hahn, and S. K. Calderwood
ix
x Contents
Role of Antioxidant Nutrients in Preventing Retinal Damage During
Hyperbaric Oxygen Treatment 91
A. L. Hollis, R. A. Henderson, and W. L. Stone
Effects of Phenylhydrazine on Human Red Cell Membrane
Aminophospholipids: A Fluorescamine Study 97
Z. Chen and A. Stern
Role of Oxygen Radicals in Peroxidation of Docosahexaenoic Acid by
Rat Brain Homogenate In Vitro 103
T. Shingu and N. Salem, Jr.
Possible Involvement of Queuine in Oxidative Metabolism 109
L. Szabo and W. R. Farkas
Cytochrome P-450 Interaction With Arachidonic Acid Hydroperoxides:
Role in Lipid Peroxidation 115
R. H. Weiss, J. L. Arnold, and R. W. Estabrook
Leakage of Fatty Acid Radicals During Lipoxygenase Catalysis 121
C. Kemal, L.-c. Yuan, and K. Laurenzo
The Mast Cell Granule: A Phospholipid Source for Prostaglandin
Synthesis 127
P. Chock and E. Schmauder-Chock
RADIATION-INDUCED CHANGES
IN EICOSANOID SYNTHESIS
Studies on Effect of Gamma Radiation on Prostacyclin and Platelet
Activating Factor Synthesis and on Cell Growth Using Smooth Muscle,
Fibroblast, and Endothelial Cells in Cultures 135
M. Menconi, L. Taylor, and P. Polgar
Prostacyclin and Thromboxane Production by Irradiated Rat Lung 147
W. F. Ward and J. M. Hinz
Eicosanoid Changes in Skin Following Ultraviolet Light Irradiation 159
V. A. Ziboh and B. Burrall
Contents xi
Leukotriene Synthesis by UV-Irradiated Macrophage Cell Cultures 173
J. E. Hardcastle and S. Minoui
Influence of Psora1en and Ultraviolet Therapy on Platelet Function and
Arachidonic Acid Metabolism in Patients With Vitiligo 179
G. H. R. Rao, M. Hordinsky, C. J. Witkop, and J. G. White
Sources of Increased In Vivo Cyclooxygenase Product Release Following
Whole-Body Irradiation of Rats 185
M. J. Schneidkraut, P. A. Kot, and P. W. Ramwell
Thermal Injury Causes Stimulation of Phospholipase A2 Activity in
Mammalian Cells 201
S. K. Calderwood, E. K. Farnum, and M. A. Stevenson
Effects of Neutron Irradiation on PGE2 and TxB2 Levels in Biological
Fluids: Modification by WR-2721 207
L. K. Steel and G. D. Ledney
Thromboxane and Prostacyclin Production by Irradiated and Perfused
Rat Kidney 219
Z. Weshler, A. Raz, E. Rosenmann, S. Biran, Z. Fuks, and A. Eldor
Generation of a Neutrophil Chemoattractant of the Lipoxygenase
Pathway by Irradiated Bovine Aortic Endothelial Cells 225
A. Eldor, M. Cohn, l. Vlodavsky, E. Razin, E. Hy-Am, Z. Fuks, and
Y. Matzner
PROSTAGLANDINS IN RADIATION
PROTECTION AND RECOVERY
Radiation Protection by Exogenous Arachidonic Acid and Several
Metabolites 233
W. R. Hanson
Alterations in Locomotor Activity Induced by Radioprotective Doses of
l6,16-Dimethyl Prostaglandin E2 245
M. R. Landauer, T. L. Walden, H. D. Davis, and J. A. Dominitz
xii Contents
Effect of PGE 2 on Radiation Response of Chinese Hamster V79 Cells
In Vitro 253
E. V. Holahan, w: F. Blakely, and T. L Walden
A Paradoxical Role for Eicosanoids: Radioprotectants and
Radiosensitizers 263
T. L Walden, Jr.
CLINICAL IMPLICATION
Eicosanoids and Elective Immunosuppression 275
P. w: Ramwell, M. L Foegh, and P. Kot
Prostaglandins and Hemopoietic Cell Recovery Following Irradiation 283
R. L DeGowin
Ionizing Radiation, Prostaglandins, and Gastric Function in Monkeys 293
A. Dubois, E. D. Dorval, N. Fiala, and L K. Steel
Changes in Renal Blood Flow, Glomerular Filtration, and Vasoactive
Hormones in Bone-Marrow-Transplant Recipients After Total-Body
Irradiation 305
S. C. Textor, S. J. Forman, R. D. Zipser, and J. E. Carlson
Eicosanoids and Radiotherapy in Human and Animal Tumors 319
L F. Stamford, J. D. Gaffen, P. B. Melhuish, and A. Bennett
Modification of Radiation Injury of Murine Intestinal Clonogenic Cells
and B-16 Melanoma by PGb or Flurbiprofen 331
w: w:
R. Hanson, Jarnagin, K. DeLaurentiis, and F. D. Malkinson
Influence of UV Light (250 nm) on Platelet Activation 339
G. H. R. Rao, C. A. Cox, C. J. Witkop, and J. G. White
Effects of Eicosanoid Precursors on TBA Reactive Material in Normal
and Malignant Cells 345
M. E. Begin, G. Ells, and D. F. Horrobin
