MORRIS HEPATOMAS Mechanisms of Regulation ADV ANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY Editorial Board: Nathan Back State University of New York at Buffalo N. R. Di Luzio Tulane University School of Medicine Bernard Halpern College de France and Institute of Immuno·Biology Ephraim Katchalski The Weizmann Institute of Science David Kritchevsky Wistar Institute Abel Lajtha New York State Research Institute for Neurochemistry and Drug Addiction Rodolfo Paoletti University of Milan Recent Volumes in this Series Volume 86A PROTEIN CROSSLINKING: Biochemical and Molecular Aspects Edited by Mendel Friedman Volume 86B PROTEIN CROSSLINKING: Nutritional and Medical Consequences Edited by Mendel Friedman Volume 87 HYPOTHALAMIC PEPTIDE HORMONES AND PITUITARY REGULATION Edited by John C. Porter Volume 88 AVIAN IMMUNOLOGY Edited by Albert A. Benedict Volume 89 MUCUS IN HEALTH AND DISEASE Edited by Max Elstein and Dennis V. Parke Volume 90 PARKINSON'S DISEASE: Neurophysiological, Clinical, and Related Aspects Edited by Fathy S. Messiha and Alexander D. Kenny Volume 91 INORGANIC AND NUTRITIONAL ASPECTS OF CANCER Edited by G. N. Schrauzer Volume 92 MORRIS HEPATOMAS: Mechanisms of Regulation Edited by Harold P. Morris and Wayne E. Criss Volume 93 IMMUNITY TO BLOOD PARASITES OF ANIMALS AND MAN Edited by Louis H. Miller, John A. Pino, and John J. McKelvey, Jr. Volume 94 OXYGEN TRANSPORT TO TISSUE - III Edited by I. A. Silver, M. Erecinska, and H. I. Bicher Volume 95 ACID PROTEASES: Structure, Function, and Biology Edited by Jordan Tang MORRIS HEPATOMAS Mechanisms of Regulation Edited by Harold P. Morris and Wayne E. Criss Department of Biochemistry and Howard Cancer Research Center Howard University Medical School Washington, D.C. PLENUM PRESS • NEW YORK AND LONDON Library of Congress Cataloging in Publication Data Hepatoma Symposium, 6th, Washington, D. C., 1977. Morris hepatomas. (Advances in experimental medicine and biology; v. 92) "Based on the proceedings of the Sixth Biennial Hepatoma Symposium held in Washington, D. C., May 22-24, 1977." Bibliography: p. Includes index. 1. Hepatoma-Congresses. 2. Oncology, Experimental-Congresses. 3. Diseases-Animal models-Congresses. I. Morris, Harold Paul, 1900- II. Criss, Wayne E. III. Title. IV. Series. RC280.L5H471977 616.9'94'36 77-13136 ISBN-13: 978-1-4615-8854-2 e-ISBN -13: 978-1-4615-8852-8 DOl: 10.1007/978-1-4615-8852-8 Based on the proceedings of the Sixth Biennial Hepatoma Symposium held in Washington, D.C., May 22-24, 1977 © 1978 Plenum Press, New York Softcover reprint of the hardcover 1st edition 1978 A Division of Plenum Publishing Corporation 227 West 17th Street, New York, N. Y. lOOn All rights 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, or otherwise, without written permission from the Publisher Preface In 1960, Dr. Van R. Potter and Dr. Henry Pitot (at McCardle Laboratory in Madison, Wisconsin), Dr. Tetsuo Ono (then at McCardle Laboratory and now at the Japanese Foundation for Cancer Research in Tokyo, Japan) and Dr. Harold P. Morris (then at the National Cancer Institute and now at Howard University, Washington, D.C.) decided that an experimental cancer model would be an invaluable tool to examine neoplastic changes in cells. Since they were study ing the various highly specific metabolic processes which are unique to liver tissues, they determined that a transplantable liver cancer model would be the ideal system to work with. This system would provide for comparison of normal liver tissue of the non-tumor bear ing animal, the tumor bearing animal's (host) liver and the liver cancer. Dr. Morris undertook a series of rat studies employing several chemicals known to cause liver cancer. Soon the first Morris hepatomas (#3683, 3924A, 5123) were being studied by several labs. During the next 18 years, Dr. Morris developed and transplanted numerous strains of hepatomas of which no two were identical. These tumors ranged from the very slowly-growing, highly differentiated cancer tissues, e.g., 96l8A which is a diploid tumor containing gly cogen and a "nearly normal" complement of enzymes, to a large group of rapidly-growing, poorly differentiated cancer tissues, e.g., 3924A and 96l8A2 (latter being derived from 96l8A) both of which are hetero ploid and have lost almost all of their complement of enzymes which carry out the differentiated functions of liver tissue. This spectrum of cancer tissues has been and is now being utilized by hundreds of laboratories located allover the world. It has provided cancer re searchers with a stable population of cancer cells for examining every parameter of molecular and cellular functioning. The spectrum of Morris hepatoma has provided us up to now with the most complete un derstanding possible of cancer tissues in action. We now know more about the "typical" cancer tissue, from the hundreds of reports on the Morris hepatomas, than from any other single cancer model system. The present book represents the first attempt to accumulate and review our knowledge about cancer as gained during the last two decades from studying the Morris hepatomas. It provides the reader v PREFACE with a beautiful example of the open sharing of scientific ideas and concepts and it elegantly demonstrates how the devoted cooperation among scientists can truly yield highly synergistic results. It gives a clearer picture of the origin, evolution, and demise of cancer theories. And it also provides the reader with a distinct preview of new cancer theories which may now be present on the horizon. We wish to sincerely thank the several hundred scientists, students and technicians who over the many years have worked with and searched out the now classical metabolism of cancer tissues, as gained from studies of the Morris hepatomas. We wish to gratefully acknow ledge the key people involved in the daily induction, transplanta tion and management of the many strains of Morris hepatomas: Billy P. Wagner (Dr. Morris' assistant at NCI for 17 years), Charity M. Jackson (Dr. Morris' assistant at Howard University for the last 10 years), Louise Lawson, Debra Richardson, Martha Mosley, Dr. David Meranze, and Dr. Leonard Slaughter. We wish also to ex press our sincere appreciation to Nur Bilge Criss for her assistance in reviewing, editing, typing and proofing this book. All senior authors were supported, in part, by USPHS Grant # 10429. Contents SECTION I: OVERVIEW OF KNOWLEDGE BY ASSESSMENTS FROM THE SYSTEM OF MORRIS "MINIMAL DEVIATION" HEPATOMAS Historical Development of Transplantable Hepatomas • • • • • 1 Harold P. Morris and Lynnard J. Slaughter Contribution of the Morris Hepatomas to the Biochemistry of Cancer- Establishment of the Phenotypic Heterogeneity of Neoplasms -In -Vi-vo •••.••.•• 21 Henry C. Pitot and James Cardelli The Morris Hepatomas as Models for Studies of Gene Expression in Neoplasia 39 Jennie B. Shatton and Sidney Weinhouse Hormonal Induction of Enzyme Functions, Cyclic AMP Levels and AlB Transport in Morris Hepatomas and in Normal Liver Systems 59 Van Rensselaer Potter The Molecular Correlation Concept of Neoplasia: Recent Advances and New Challenges • • 89 George Weber, Harutoshi Kizaki, Taiichi Shiotani, Diana Tzeng, and Jim C. Williams Expression Mechanisms of Abnormality of Ornithine Aminotransferase Level in Morris Hepatoma 117 Nobuhiko Katunuma and Keiko Kobayashi vii viii CONTENTS SECTION II: NUCLEAR COMPOSITION Controls of Nucleolar Function in Cancer Cells • . • . • 125 Harris Busch, N.R. Ballal, R.K. Busch, Y.C. Choi, F. Davis, I.L. Goldknopf, S.I. Matsui, M.S. Rao, and L. I. Rothblum Nuclear Macromolecular Changes in Hepatomas 181 Jen-Fu Chiu, Labouir S. Hnilica, Luc Belanger, and Harold P. Morris Enzymatic Modification of Nuclear Proteins During Neoplastic Growth • • • • • • • . 205 Woon Ki Paik, Samuel Nochumson and Sangduk Kim SECTION III: REGULATIONS OF NUCLEAR FUNCTIONING Regualtion of DNA Synthesis in Isolated Morris Hepatoma Nuclei . • • • 233 Peter Ove and Mona L. Coetzee DNA-Dependent RNA Polymerases from Morris Hepatomas 3924A and 7800 and from Liver Treated with Thioacetamide • • • • • • • • • . . • 273 Samson T. Jacob, Kathleen M. Rose, Thomas B. Leonard, and Barry Duceman Regulation of Macromolecular Syntheis in Morris Hepatomas •....• 289 Michael A. Lea Control of Specific Messenger RNA Species in Liver and Hepatoma . • 307 Philip Feigelson and Linda W. DeLop SECTION IV: INTRACELLULAR ORGANELLES AND MEMBRANES Alterations in Peroxisomes of Hepatomas 331 Hideyuki Tsukada, Yohichi Mochizuke and Mikio Gotoh CONTENTS ix Hexokinase: The Direct Link Between Mitochondrial and Glycolytic Reactions in Rapidly Growing Cancer Cells • • • • • • • • • ". 363 Ernesto Bustamante, Harold P. Morris and Peter L. Pedersen The Composition and Metabolism of Microsomal and Mitochondrial Membrane Lipids in the Morris 7777 Hepatoma • • • • • • • • • • • •• 381 Richard Morton, Moseley Waite, John W. Hartz, Carol Cunningham, and Harold P. Morris Terminal Sugars in Glycoconjugates: Metabolism of Free and Protein Bound L-Fucose, N-Acetylneuraminic Acid, and D-Galactose in Liver and Morris Hepatomas • • • • • 405 W. Reutter and C. Bauer Surface Membranes and Biological Regulation in Differentiated Hepatoma Cells In Vitro 439 Carnia Borek SECTION V: REGULATION OF CYTOPLASMIC FUNCTIONING Regualtion of Cyclic AMP and Cyclic GMP in Morris Hepatomas and Liver • • • 451 Robert A. Hickie Cyclic Nucleotide Metabolism in Solid Tumor Tissues • • • • 489 Wayne E. Criss, Perpetua Muganda, Atul Sahai, and Harold P. Morris Transfer RNA in Hepatomas • • • • • • • • • • • • • • 517 E. Randerath, A.S. Gopalakrishnan, and K. Randerath The Synthesis and Secretion of Serum Albumin in Morris Hepatomas 5l23tc and 9121 565 Gerhard Schreiber, JBrg Urban, Heide Dryburgh, and T.R. Bradley Loss of Regulation of Lipid Metabolism in Morris Hepatomas: A Potential Role for Cytoplasmic Binding Proteins 583 S. Mishkin and M.L. Halperin x CONTENTS SECTION VI: VITAHINS, MINERALS, AND DIET Vitamin B6 Effect on the Growth of Morris Hepatomas and the Development of Enzymatic Activity 607 George P. Tryfiates Iron and Copper Metabolism in Cancer, as Exemplified by Changes in Ferritin and Ceruloplasmin in Rats with Transplantable Tumors • Haria C. Linder Abnormal Dietary Regulation of Glutamine Synthetase in Morris Hepatomas . • • . . 665 Thomas F. Deuel, Marjorie Louie, and Harold P. Morris SECTION VII: rXPERlMENTAL THERAPY :;0] jd Tumor Models for the Assessment of Different Treatment Modalities: Perturbations in the Kinetics of Tumor and Host Organ Cellular Regulation Demonstrated by Single and Combined Experimental Therapy 677 W.B. Looney, H.A. Hopkins, and J.S. Trefil Special Bibliography of Hepatoma CeJl Lines 759 JJld ex 77]