Cancer: Cell Structures, Carcinogens and Genomic Instability Edited by Leon P. Bignold Birkhäuser Verlag Basel · Boston · Berlin Editor Leon P. Bignold Division of Tissue Pathology Institute of Medical and Veterinary Science PO Box 14 Rundle Mall,SA 5001 Australia Library of Congress Cataloging-in-Publication Data Cancer :cell structures,carcinogens and genomic instability / edited by Leon P. Bignold. p. ; cm. -- (EXS ; 96) Includes bibliographical references and index. ISBN-13:978-3-7643-7156-2 (alk. paper) ISBN-10:3-7643-7156-0 (alk. paper) 1. Carcinogenesis--Molecular aspects. 2. Cancer cells. 3. Cancer--Pathophysiology. 4. Cancer--Genetic aspects. I. Bignold,Leon P.,1947- II. Series [DNLM:1. Neoplasms--genetics. 2. Carcinogens-adverse effects. 3. Gene Expression Regulation, Neoplastic--drug effects. 4. Genomic Instability. 5. Neoplasms-etiology. QZ202 C21518 2005] RC268.5.C28 2005 616.99'4071--dc22 2005048329 Bibliographic information published by Die Deutsche Bibliothek Die Deutsche Bibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data is available in the Internet at <http://dnb.ddb.de>. ISBN 10:3-7643-7156-0 Birkhäuser Verlag,Basel – Boston – Berlin ISBN 13:978-3-7643-7156-2 The publisher and editor can give no guarantee for the information on drug dosage and administration contained in this publication. The respective user must check its accuracy by consulting other sources of reference in each individual case. The use of registered names,trademarks etc. in this publication,even if not identified as such,does not imply that they are exempt from the relevant protective laws and regulations or free for general use. This work is subject to copyright. All rights are reserved,whether the whole or part of the material is concerned,specifically the rights of translation,reprinting,re-use of illustrations,recitation,broad- casting,reproduction on microfilms or in other ways,and storage in data banks. For any kind of use, permission of the copyright owner must be obtained. ©2006 Birkhäuser Verlag,P.O. Box 133,CH-4010 Basel,Switzerland Part of Springer Science+Business Media Printed on acid-free paper produced from chlorine-free pulp. TCF ∞ Cover illustration:Bottom right:Somatic translocations and mis-targeting of HATs and HDACs (see Fig. 2,p. 27,detail). Bottom left:Proposed dose-response relationship for radiation-induced effects (see Fig. 1, p.168). Top right: Bioactivation of aromatic amines or amides (AA) towards ultimate DNA-reactive sulphate or acetoxy esters (see Fig. 3, p. 71, detail). Top left:A typical metaphase spread from a fifth generation (G5) mTERC–/–mouse fibroblast showing a fusion product (arrow) and 41 chromosomal arms,an example of aneuploidy (see Fig. 3,p. 56). Printed in Germany ISBN 10:3-7643-7156-0 e-ISBN:3-7643-7378-4 ISBN 13:978-3-7643-7156-2 9 8 7 6 5 4 3 2 1 www. birkhauser.ch V Contents List of Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . VII Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . XI Leon P. Bignold,B. L. D. Coghlan and H. P. A. Jersmann Cancer morphology,carcinogenesis and genetic instability: a background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Bojan Drobic,Katherine L. Dunn,Paula S. Espino and James R. Davie Abnormalities of chromatin in tumor cells . . . . . . . . . . . . . . . . . . . . . 25 Sen Pathak and Asha S. Multani Aneuploidy,stem cells and cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Andreas Luch The mode of action of organic carcinogens on cellular structures . . . 65 Troy R. Durham and Elizabeth T. Snow Metal ions and carcinogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 David I. Pattison and Michael J. Davies Actions of ultraviolet light on cellular structures . . . . . . . . . . . . . . . . 131 Carmel Mothersill and C. B. Seymour Actions of radiation on living cells in the “post-bystander”era . . . . . 159 Karl Münger,Hiroyuki Hayakawa,Christine L. Nguyen, Nadja V. Melquiot,Anette Duensing and Stefan Duensing Viral carcinogenesis and genomic instability . . . . . . . . . . . . . . . . . . . 179 Herman H. Cheung,Vinay Arora,Robert G. Korneluk Abnormalities of cell structures in tumors:apoptosis in tumors . . . . . 201 Jay Harper and Marsha A. Moses Molecular regulation of tumor angiogenesis:mechanisms and therapeutic implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223 VI Contents Okio Hino,Toshiyuki Kobayashi and Kazuo Okimoto Genetic and environmental factors in hereditary predisposition to tumors:a conceptual overview . . . . . . . . . . . . . . . . . . . . . . . . . . . 269 Marianne Sowa,Benjamin J. Arthurs,Brian J. Estes and William F. Morgan Effects of ionizing radiation on cellular structures,induced instability and carcinogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293 Stavroula Raptis and Bharati Bapat Genetic instability in human tumors . . . . . . . . . . . . . . . . . . . . . . . . . 303 William B. Coleman and Gregory J. Tsongalis Molecular mechanisms of human carcinogenesis . . . . . . . . . . . . . . . . 321 Assam El-Osta Mechanisms of abnormal gene expression in tumor cells . . . . . . . . . . 351 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 VII List of Contributors Vinay Arora, Apoptosis Research Centre, Children’s Hospital of Eastern Ontario, Research Institute, 401 Smyth Road, Ottawa, Ontario K1H 8L1, Canada; e-mail:[email protected] Benjamin J. Arthurs, Chemical Structure & Dynamics, Pacific Northwest National Laboratory, MS K8-88, 3335 Q Ave, Richland,WA 99354, USA; e-mail:[email protected] Bharati Bapat,Samuel Lunenfeld Research Institute,Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, 9th Floor, Room 992B, Toronto, Ontario M5G 1X5, Canada; and Department of Laboratory Medicine and Pathobiology, University of Toronto,Toronto,ON,M5S1A1,Canada; e-mail:[email protected] Leon P. Bignold, Division of Tissue Pathology, Institute of Medical and Veterinary Science, PO Box 14, Rundle Mall, SA 5001,Australia; e-mail: [email protected] Herman H. Cheung, Apoptosis Research Centre, Children’s Hospital of Eastern Ontario,Research Institute,401 Smyth Road,Ottawa,Ontario K1H 8L1,Canada; e-mail:[email protected] B. L. D. Coghlan, Centre for European Studies and General Linguistics, University of Adelaide,Adelaide,SA 5005,Australia William B. Coleman,Department of Pathology and Laboratory Medicine,UNC Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Campus Box 7525, Room 515, Brinkhous-Bullitt Building, Chapel Hill, NC 27599, USA; e-mail: william.coleman@ pathology.unc.edu James R. Davie, Manitoba Institute of Cell Biology, 675 McDermot Avenue, Winnipeg,Manitoba,R3E 0V9 Canada; e-mail:[email protected] Michael J. Davies, The Heart Research Institute, 145 Missenden Road, Camperdown,Sydney,NSW 2050,Australia; e-mail:[email protected] Bojan Drobic, Manitoba Institute of Cell Biology, 675 McDermot Avenue, Winnipeg,Manitoba,R3E 0V9 Canada; e-mail:[email protected] Anette Duensing, Molecular Virology Program, University of Pittsburgh Cancer Institute,Hillman Cancer Center,Research Pavillion,Suite 1.8,5117 Centre Avenue,Pittsburgh,PA 15213,USA; e-mail:[email protected] Stefan Duensing, Molecular Virology Program, University of Pittsburgh Cancer Institute,Hillman Cancer Center,Research Pavillion,Suite 1.8,5117 Centre Avenue,Pittsburgh,PA 15213,USA; e-mail:[email protected] Katherine L. Dunn,Manitoba Institute of Cell Biology,675 McDermot Avenue, Winnipeg,Manitoba,R3E 0V9 Canada; e-mail:[email protected] VIII List of contributors Troy R. Durham, Centre for Cellular and Molecular Biology, School of Biological and Chemical Sciences, Deakin University, 221 Burwood Highway,Burwood,Victoria 3125,Australia; e-mail:[email protected] Assam El-Osta, The Alfred Medical Research and Education Precinct (AMREP),Baker Medical Research Institute,Epigenetics in Human Health and Disease Laboratory,Second Floor,Commercial Road,Prahran,Victoria 3181,Australia; e-mail:[email protected] Paula S. Espino, Manitoba Institute of Cell Biology, 675 McDermot Avenue, Winnipeg,Manitoba,R3E 0V9 Canada; e-mail:[email protected] Brian J. Estes, Chemical Structure & Dynamics, Pacific Northwest National Laboratory, MS K8-88, 3335 Q Ave, Richland, WA 99354, USA; e-mail: [email protected] Jay Harper, Vascular Biology Program, Children’s Hospital Boston, Karp Research Building 12.214, 300 Longwood Avenue, Boston, MA 02115, USA; and Department of Surgery, Harvard Medical School, Boston, MA 02115,USA; e-mail:[email protected] Hiroyuki Hayakawa, The Channing Laboratory, Room 861, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA 02115, USA; e-mail:[email protected] Okio Hino, Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; e-mail: [email protected] H.P.A. Jersmann, Department of Medicine, University of Adelaide,Adelaide, SA 5005,Australia; e-mail:[email protected] Toshiyuki Kobayashi, Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; e-mail: [email protected] Robert G. Korneluk, Apoptosis Research Centre, Children’s Hospital of Eastern Ontario,Research Institute,401 Smyth Road,Ottawa,Ontario K1H 8L1,Canada; e-mail:[email protected] Andreas Luch, Massachusetts Institute of Technology, Center for Cancer Research, 77 Massachusetts Avenue, E17-132, Cambridge, MA 02139, USA; e-mail:[email protected] Nadja V. Melquiot, The Channing Laboratory, Room 861, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA 02115, USA; e-mail:[email protected] William F. Morgan, Radiation Oncology Research Laboratory, BRB 7-011, and Greenebaum Cancer Center, University of Maryland, Baltimore, Baltimore,MD 21201-1551,USA; e-mail:[email protected] Marsha A. Moses, Vascular Biology Program, Children’s Hospital Boston, Karp Research Building 12.214, 300 Longwood Avenue, Boston, MA 02115,USA; and Department of Surgery,Harvard Medical School,Boston, MA 02115,USA; e-mail:[email protected] Carmel Mothersill, Medical Physics and Applied Radiation Sciences Unit, McMaster University, Hamilton, Ontario L8S 4K1, Canada; e-mail: List of contributors IX [email protected] Karl Münger, The Channing Laboratory, Room 861, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA 02115, USA; e-mail: [email protected] Asha S. Multani, Department of Molecular Genetics, Unit # 011, The University of Texas M. D. Anderson Cancer Center,1515 Holcombe Blvd., Houston,TX 77030,USA Christine L. Nguyen, The Channing Laboratory, Room 861, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA 02115, USA; e-mail:[email protected] Kazuo Okimoto,Toxicology Group,Safety Research Laboratories,Dainippon, Pharmaceutical Co.,Ltd.,33-94,Enoki-cho,Suita,Osaka 564-0053,Japan; e-mail:[email protected] Sen Pathak,Department of Molecular Genetics,Unit # 011,The University of Texas M. D. Anderson Cancer Center,1515 Holcombe Blvd.,Houston,TX 77030,USA; e-mail:[email protected] David I. Pattison, The Heart Research Institute, 145 Missenden Road, Camperdown,Sydney,NSW 2050,Australia; e-mail:[email protected] Stavroula Raptis, Samuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine,Mount Sinai Hospital,600 University Avenue, 9th Floor, Room 992B, Toronto, Ontario M5G 1X5, Canada; and Department of Laboratory Medicine and Pathobiology, University of Toronto,Toronto,ON,M5S1A1,Canada; e-mail:[email protected] Marianne Sowa,Chemical Structure & Dynamics,Pacific Northwest National Laboratory, MS K8-88, 3335 Q Ave, Richland, WA 99354, USA; e-mail: [email protected] C. B. Seymour, Medical Physics and Applied Radiation Sciences Unit, McMaster University,Hamilton,Ontario L8S 4K1,Canada Elizabeth T. Snow, Centre for Cellular and Molecular Biology, School of Biological and Chemical Sciences, Deakin University, 221 Burwood Highway,Burwood,Victoria 3125,Australia; e-mail:[email protected] Gregory J. Tsongalis, Laboratory of Molecular Pathology, Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA XI Preface This volume began with an invitation from the publishers to edit a volume of EXS on Cancer. This invitation undoubtedly derived from my articles in Cellular and Molecular Life Sciences in 2002 and 2003 on the relationships between the morphology,aetiology and pathogenesis of tumours,especially in relation to genetic instability. After many years of teaching the theories of can- cer in undergraduate medical school courses,it seemed to me that the variably chaotic histopathologic features of tumours parallel in some way,the variably unstable genomes of tumour cells,which were being discovered in the 1990s. Thus the title of the volume has come to include morphology, carcinogenesis and genetic instability. The invitation came while I was working with Herrn Dr. med. Hubertus Jersmann (MD Düsseldorf, PhD, now Senior Lecturer in Medicine of the University of Adelaide) and Professor Brian Coghlan (Emeritus Professor of German, the University of Adelaide), on the work of the nineteenth century cancer pathologists,especially David Paul von Hansemann (1858–1920). With the delivery of the manuscripts from the authors of the chapters, it became obvious that a background chapter for the volume could include some of the material which we had “uncovered” together. Because of this, chapter 1 is authored by the three of us,and the “new”material figures prominently. I am extremely grateful to the contributors of the chapters, without whom, of course there could be no volume at all,and to Dr. Beatrice Menz,the super- vising editor at Birkhäuser,who has been unfailingly helpful and patient. The staff of the Barr-Smith Library at the University of Adelaide were very helpful throughout and Mr. Peter Dent of the Photography Department of the Institute of Medical and Veterinary Science,Adelaide,assisted with the design of the cover. Leon P. Bignold March 2005