MECHANISMS OF DNA DAMAGE AND REPAIR

Implications for Carcinogenesis and Risk Assessment

BASIC LIFE SCIENCES Alexander Hollaender, General Editor Council for Research Planning in Biological Sciences, Inc., Washington, D.C.

Recent volumes in the series:

Volume 29 SISTER CHROMATID EXCHANGES: 25 Years of Experimental Research Part A: The Nature of SCEs Part B: Genetic Toxicology and Human Studies Edited by Raymond R. Tice and Alexander Hollaender

Volume 30 PLASMIDS IN BACTERIA Edited by Donald R. Helinski, Stanley N. Cohen, Don B. Clewell, David A. Jackson, and Alexander Hollaender

Volume 31 GENETIC CONSEQUENCES OF NUCLEOTIDE POOL IMBALANCE Edited by Frederick J. de Serres

Volume 32 TISSUE CULTURE IN FORESTRY AND AGRICULTURE Edited by Randolph R. Henke, Karen W. Hughes, Milton J. Constantin, and Alexander Hollaender

Volume 33 ASSESSMENT OF RISK FROM LOW-LEVEL EXPOSURE TO RADIATION AND CHEMICALS: A Critical Overview Edited by Avril D. Woodhead, Claire J. Shellabarger, Virginia Pond, and Alexander Hollaender

Volume 34 BASIC AND APPLIED MUTAGENESIS: With Special Reference to Agricultural Chemicals in Developing Countries Edited by Amir Muhammed and R. C. von Borstel

Volume 35 MOLECULAR BIOLOGY OF AGING Edited by Avril D. Woodhead, Anthony D. Blackett, and Alexander Hollaender

Volume 36 ANEUPLOIDY: Etiology and Mechanisms Edited by Vicki L. Dellarco, Peter E. Voytek, and Alexander Hollaender

Volume 37 GENETIC ENGINEERING OF ANIMALS: An Agricultural Perspective Edited by J. Warren Evans and Alexander Hollaender

Volume 38 MECHANISMS OF DNA DAMAGE AND REPAIR: Implications for Carcinogenesis and Risk Assessment Edited by Michael G. Simic, Lawrence Grossman, and Arthur C. Upton

A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher.

MECHANISMS OF DNA DAMAGE AND REPAIR

Implications for Carcinogenesis and Risk Assessment

Edited by

Michael G. Simic National Bureau of Standards

Gaithersburg, Maryland and Chemistry Department

American University

Washington, D.C.

Lawrence Grossman Johns Hopkins University

Baltimore, Maryland

and

Arthur C. Upton New York University Medical Center

New York, New York

Publications Coordinator Assistant Editor

Caprice M. Chappas David S. Bergtold

PLENUM PRESS • NEW YORK AND LONDON

Library of Congress Cataloging in Publication Data

Mechanisms of DNA damage and repair.

(Basic life sciences: v. 38) Based on papers presented at a conference held at the National Bnreau of Standards in

Gaitherburg, Md. on June 2-7, 1985, and sponsored by the bureau and other agencies. Includes bibliographies and index. 1. Carcinogenesis-Congresses. 2. Deoxyribonucleic acid-Decay-Congresses. 3. De­

oxyribonucleic acid repair-Congresses. 4. Health risk assessment-Congresses. i. Simic, Michael G. 11. Grossman, Lawrence, 1924- . Ill. Upton, Arthur C. IV. United States.

National Bureau of Standards. V. Series. [DNLM: 1. Carcinogens-congresses. 2. DNA

Repair - congresses. 3. Mutagens - congresses. 4. Probability - congresses. 5. Radiation In­juries-congresses. W3 BA255 v.38/QZ 202 M48545 1985] RC268.5.M434 1986 616.94'4071 86-9363

Proceedings of a symposium on Mechanisms of DNA Damage and Repair: Implications for Carcinogenesis and Risk Assessment,

held June 2-7,1985 in Gaithersburg, Maryland

© 1986 Plenum Press, New York

Softcover reprint of the hardcover 1st edition 1986

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 in any form or by any means, electronic, mechanical, photocopying, microfilming,

recording, or otherwise, without written permission from the Publisher

Lihrary of Congress Cataloging in Puhlication Data

Mechanisms of DNA damage and repair.

(Basic life sciences: v. 38) Based on papers presented at a conference held at the National Bnreau of Standards in

Gaitherhurg, Md. on June 2-7, 1985, and sponsored hy the hureau and other agencies. Includes hihliographies and index. 1. Carcinogenesis-Congresses. 2. Deoxyrihonucleic acid-Decay-Congresses. 3. De­

oxyrihonucleic acid repair-Congresses. 4. Health risk assessment-Congresses. i. Simic,

Michael G. 11. Grossman, Lawrence, 1924- . 111. Upton, Arthur C. IV. United States.

National Bureau of Standards. V. Series. [DNLM: 1. Carcinogens-congresses. 2. DNA

Repair - congresses. 3. Mutagens - congresses. 4. Prohahility - congresses. 5. Radiation In­juries-congresses. W3 BA255 v.38/QZ 202 M48545 1985]

RC268.5.M434 1986 616.94'4071 86-9363

ISBN 978-1-4615-9464-2 ISBN 978-1-4615-9462-8 (eBook) DOI 10.1007/978-1-4615-9462-8

Proceedings of a symposium on Mechanisms of DNA Damage and Repair: Implications for Carcinogenesis and Risk Assessment,

held June 2-7,1985 in Gaithershurg, Maryland

© 1986 Plenum Press, New York

Softcover reprint ofthe hardcover 1st edition 1986

A Division of Plenum Puhlishing Corporation 233 Spring Street, New York, N.Y. 10013

All rights reserved

No part of this hook may he reproduced, stored- in a retrieval system, or transmitted in any form or hy any means, electronic, mechanical, photocopying, microfilming,

recording, or otherwise, without written permission from the Puhlisher

DNA is the beginning and the end.

vi

SPONSORS

National Bureau of Standards

International Life Sciences Institute

National Cancer Institute

National Institute of Environmental Health Sciences

National Institute of General Medical Sciences

Department of Energy

U. S. Army Medical R&D Command

American Cyanamid Company

American Industrial Health Council

Shell Development Company

Diamond Shamrock

Dow Chemical U. S. A.

E. I. du Pont de Nemours & Company

Hoffman-LaRoche

The Upjohn Company

Bristol-Myers

Burroughs Well come Company

Merck Sharp and Dohme

PREFACE

This book is based on the papers presented at the conference on "Mecha­nisms of DNA Damage and Repair: Implications for Carcinogenesis and Risk Assessment," held at the National Bureau of Standards on June 2-7, 1985, This volume deals with mechanisms of DNA damage and repair at the molecular level; consequences of unrepaired or misrepaired damage, with major emphasis on carcinogenesis; drugs which bind selectively to altered and potentially damaging DNA sequences; and potential utilization of DNA damage as an endpoint for assessing risks of UV light, ionizing radiations, chemicals, drugs, and hazardous agents in foods.

Because the induction of mutations by radiation and genotoxic chemicals has been observed to follow one-hit kinetics in some instances, it is generally assumed that any level of exposure to a DNA-damaging agent may increase the risk of genetic disease or cancer in an exposed population. At the same time, however, there is evidence that although the DNA of living cells is continually damaged by natural background radiation, free radicals, and other naturally occurring processes, most of the damage is normally repaired.

Knowledge of the intricate relationships between the toxicity of hazardous agents and the level of exposure, possible synergistic effects of exposure to other agents, damage to DNA and its repair or misrepair, repair capacity of the affected cells, and the factors influencing the processes of damage and repair at various stages in their evolution are essential for understanding molecular carcinogenesis and for developing scientifically based risk assess­ment. The need for further knowledge of these processes is pressing in view of the wide use of genotoxicity assays as screening tests, the uncertainties involved in interpreting such tests in our present state of knowledge, and the health and economic implications of positive or negative test results. The conference was organized primarily to address this need and to highlight opportunities for research in related fields.

The articles include the latest unpublished observations by the authors. Only 59 of the 159 papers presented at the conference could be included in a book intended to provide didactic material for a general audience. These up-to-date reviews make this book particularly useful to research scientists in cancer etiology, cancer therapy, and cancer prevention. The book should also be of interest to biochemists, molecular biologists, radiation chemists and biologists, free-radical chemists, food chemists, and toxicologists. In addition, it is useful background material for those engaged in risk assessment and regulatory decision-making.

Michael G. Simic

Larry Grossman

Arthur D. Upton

ACKNOWLEDGEMENTS

Contributions and assistance of the Organizing Committee: Donald R. Johnson, NBS; Curt Reimann, NBS; Sanford A. Miller, FDA; David G. Longfellow, NCI; Enrico Clementi, IBM; Michael Kssha, Florida State University; Peter A. Cerutti, Swiss Institute for Experimental Cancer Research; George Scholes, University of Newcastle on Tyne; J. Martin Brown, Stanford University; E. Larry Powers, University of Texas; and the Session Chairmen: Dietrich Schulte­Frohlinde, Max Planck Institute; J. William Lown, University of Alberta; Jean-Bernhard LePecq, Institute Gustav-Roussy; Kurt W. Kohn, NCI; John F. Ward, University of California San Diego; Tomas Lindahl, Imperial Cancer Research Fund; Franklin Hutchinson, Yale University; Steven R. Tannenbaum, MIT; Peter N. Magee, Temple University; Bernard D. Goldstein, Rutgers Uni­versity; W. Gary Flamm, FDA; and Nancy L. Oleinick, Case Western Reserve University.

Special thanks go to Ernest Ambler, Director of NBS; Raymond G. Kammer, Deputy Director of NBS; Sanford A. Miller, Director, Center for Food Safety and Applied Nutrition; and Richard H. Adamson, Director of Cancer Etiology; for their interest, encouragement and assistance.

Technical and management assistance of Janet N. Hauber, Conference Coordinator, Karen A. Taylor, ILSI and the NBS staff: Dene Hocken, Gloria Wiersma, Francis Weygand, Sara R. Torrence, Kathy D. Kilmer and Kathy C. Stang has been greatly appreciated.

Lastly, appreciation and acknowledgement go to those directly involved in putting this book together: Caprice Chappas, Publications Coordinator; David Bergtold, Assistant Editor; Eleanore Cordisco, Denise Sgroi, and Martha Grey, word processing.

CONTENTS

INTRODUCTION

Introduction to Mechanisms of DNA Damage and Repair Michael G. Simic

1

History of Radiation Biology from a Personal Point of View • • • • •• 9 Alexander Hollaender

DNA DAMAGE

Mechanisms of Damage

Comparison of Mechansms for DNA Strand Break Formation by the Direct and Indirect Effect of Radiation

Dietrich Schulte-Frohlinde

Eletron Spin Resonance Studies of the Mechanism of Radiation Damage to DNA •• • • . • • • • • • • • • • • •

Paul M. Cullis and Martyn C. R. Symons

Free Radical Mechanisms of DNA Base Damage Michael G. Simic and Slobodan V. Jovanovic

Peroxyl Radicals of Nucleic Acids and Their Components Clemens von Sonntag

Radiation-Induced Peroxidation of DNA and Effects of Redox-Active Agents •••• • • • • • • • • • • • •

Jane E. Frew, Peter Jones and George Scholes

The Radiation Chemistry of the Purine Bases Within DNA and Related Model Compounds ••••••••

Jean Cadet, Maurice Berger and Anthony Shaw

Bacteriophage DNA as a Model for Correlation of Radical Damage to DNA and Biological Effects • • • • • • •

Joh. Blok and H. Loman

19

29

39

51

61

69

75

xi

Damage in Cells

Ultrafast Chemical Repair of DNA Single and Double Strand Break Precursors in Irradiated V79 Cells •

Barry D. Michael, Susan Davies and Kathryn D. Held

Assessment of DNA Damage by Filter Elution Assays Kurt W. Kohn

DNA Modification by Sulfur Mustards and Nitrosoureas and Repair of These Lesions • • • • • • • • • • •

David B. Ludlum and Bruno Papirmeister

89

101

119

Intragenomic Localization of Carcinogen-DNA Damage • • • • • • • • •• 127 G. N. Wogan and G. McMahon

Ionizing Radiation Induced DNA Damage: Identities and DNA Repair •••• • • • •

John F. Ward

Effects of LETro on the Fate of DNA Damage Induced in Rabbit Sensory Cells In Situ: Fundamental Aspects •••••

J. T. Lett, D. S.lBergtold and P. C. Keng

Radiation Damage to DNA in Various Animal Tissues: A Comparison of Yields and Repair In Vivo and In Vitro

Raymond E. Meyn, W. Timothy Jenkins-an~vid Murray---

Differential Regulation of Base and Nucleotide Excision Repair in Mammalian Cells . . . . . . . . . . .

Klaus Erixon

Immediate and Repair Induced DNA Double Strand Breaks in Mammalian Cells . . . . . . . . . .

Peter E. Bryant

DNA-Protein Cross-Links: New Insights into their Formation and Repair in Irradiated Mammalian Cells • • • • •

Nancy L. Oleinick, Song-mao Chiu, Libby R. Friedman, Liang-yan Xue and Narayani Ramakrishnan

.

.

DNA-to-Protein Crosslinks and Backbone and Near-Ultraviolet and Visible Mammalian Cells • • • • • •

Meyrick J. Peak and Jennifer G. Peak

Breaks Caused by Far­Light Radiations in

DNA Binding Drugs

Sequence Specificity and Biological Consequences of Drugs that Bind Covalently in the Minor Groove of DNA

Laurence H. Hurley and Donald R. Needham-VanDevanter

Molecular Recognition of DNA Binding Agents: High-Field IH and 31p One- and Two-Dimensional NMR Studies on the 1:1 Intercalation Complexes of Mitoxantrone with Selected

135

139

151

. . . . 159

. . . . . 171

181

193

203

Oligodeoxyribonucleotides •••• • • • • • • • • • • • 211 Albin Otter, Christopher C. Hanstock, George Kotovych, Bernard

Rayner, Jacques J. Vasseur, Jean-Louis Imbach and J. W. Lown

DNA Binding and Biological Properties of Bis and Tris Intrcalating Molecules • • • • • • • • • • • • •

Jean-Bernard LePecq and Bernard P. Roques

Novel Types of DNA-Sugar Damage in Neocarzinostatin Cytotoxicity

219

and Mutagenesis ••••••••.•••.••••.••• 231 Irving H. Goldberg

DNA-Drug Binding and Control of Genetic Information • • • • • • • •• 245 Richard E. Dickerson

Computer-Aided Design of New DNA Intercalators • • • • • • • • • • •• 257 Stephen Neidle

DNA REPAIR AND CONSEQUENCES

Differential Expression of SOS Genes in an [. Coli Mutant Producing Unstable LexA Protein Enhances Excision Repair But Inhibits Mutagenesis • • • • • • • • • • • •

Kenneth R. Peterson, Ann K. Ganesan and David W. Mount

Mutagenic DNA Repair in Bacteria: The Role of UmuDC and MucAB Lorraine Marsh and Graham C. Walker

The Repair of Pyrimidine Dimers Via a DNA-Glycosylase Mechanism Robert H. Grafstrom

The Involvement of an E. Coli Multiprotein Complex in the Complete Repair of UV-Damaged DNA • • • •

Lawrence Grossman, Paul R. Caron and Euk Y. Oh

Pyrimidine Dimer Induced Alteration of DNA Tertiary Structure Evidence for Unwinding and Shortening •••••••••

Antonia M. Pedrini, Silvia Tornaletti, Paola Menichini and Angelo Abbondandolo

Mismatch Correction Paul Modrich

Molecular Approaches to the Study of Nucleotide Excision

265

273

281

287

295

303

Repair in Eukaryotes • • • • • • • • • • • • • • • • 311 E. C. Friedberg, D. P. Barbis, J. M. Chenevert, R. Fleer,

D. Kalainov, L. Naumovski, C. M. Nicolet, G. W. Robinson, R. A. Schultz, W. A. Weiss and E. Yang

Restoration of DNA Repair in UV-Sensitive Chinese Hamster Ovary Cell by the denV Gene from Bacteriophage T4 • • • • • •• 319

Kristoffer Valerie, Jon K. de Riel and Earl E. Henderson

The Adaptive Response of Mammalian Cells to Alkylating Agents Leona Samson

DNA Glycosylases in DNA Repair • • • • Tomas Lindahl

Apurinic Sites as Common Intermediates in Mutagenesis Lawrence A. Loeb, Bradley D. Preston, Elizabeth T. Snow

and Roeland M. Schaaper

327

335

341

xiii

The Repair of Uracil-Containing DNA Bernard Weiss and Hiyam H. EI-Hajj

Metabolic Consequences of DNA Damage: The Role of Poly (ADP­Ribose) Polymerase as Mediator of the Suicide Response •

Nathan A. Berger and Sosamma J. Berger

DNA Damage, DNA Repair and Induced Mutagenesis: Some Enzymological and Structural Considerations

Miroslav Radman

Mechanisms of Mutagenesis of E. Coli by Ultraviolet Light Franklin Hutchinson and Richard D. Wood

Activation of H-ras-l Oncogenes by Chemical Carcinogens Helmut Zarbl,-saraswati Sukumar, Anne L. Arthur, Dionisio

Martin-Zanca and Mariano Barbacid

Activation of the c-~ Oncogene Michael D. Cole

Salmonella Tester Strains: Mutational Targets and Correlation with Animal Carcinogenicity and Teratogenicity • • • • •

Philip E. Hartman and Sharon Lea Aukerman

Mechanisms of Spontaneous Mutagenesis: Clues from Mutational Specificity ••• • • • •

Barry W. Glickman, Douglas F. Fix, Fumio Yatagai, Philip A. Burns and Roel M. Schaaper

RISK ASSESSMENT

Use of Gradient Denaturing Gels to Determine Mutational Spectrum in Human Cells • . .• ••.•.•

Neal F. Cariello and William G. Thilly

Urinary N-Nitrosamino Acids as Indices of Endogenous Formation of N-Nitroso Compounds • . • • • • • • • • • • •

H. Ohshima, B. Pignatelli, J. Nair, N. Munoz, S. Calmels, M. Crespi, S. H. Lu, S. V. Bhide, P. Vincent, H. Leclerc, S. Kamiyama and H. Bartsch

Application of Monoclonal Antibodies to Monitor Human Exposure to Aflatoxin Bl • . • • • • • . • • • •

John D. Groopman

Blood Proteins as Carcinogen Dosimeters Steven R. Tannenbaum and Paul L. Skipper

Development of an Avidin-Biotin Amplified Enzyme-Linked Immunoassay for Detection of DNA Adducts of the Human Bladder Carcinogen 4-Aminobiphenyl • • • •

Dean W. Roberts, R Wayne Benson, Thomas J. Flammang and Fred F. Kudlubar

Intragenomic Heterogeneity in DNA Damage Processing: Potential Implications for Risk Assessment • •

Philip C. Hanawalt

349

357

365

377

385

399

407

425

439

453

463

473

479

489

The Role of Pharmacokinetics in Risk Assessment •• • • Richard H. Reitz, Tony R. Fox and Philip G. Watanabe

Immunologic Quantification of Carcinogn-DNA Adducts Regina M. Santella, Ling Ling Hsieh and Frederica Perera

Interpretation of Genotoxicity Data in Assessing the Risks of Genetic Diseases • • • • • • . . •

Carter Denniston

Background Levels of DNA Damage in the Population Robert L. Saul and Bruce N. Ames

Use of Models in Low-Dose Extrapolation John Van Ryzin

Problems in Interspecies Comparisons Richard Wilson and Edmund A. C. Crouch

The Time to Tumor Approach in Risk Assessment Roy E. Albert

The Role of Nutritional Factors in Cellular Protection Against DNA Damage, Altered Gene Expression and Malignant Transformation • • • • • • • • • • • • • • • • • • • • •

Carmia Borek

The Role of Risk Assessment in Food Safety Policy Robert J. Scheuplein

Contributors

Index

499

509

519

529

537

543

551

557

563

573

575

xv