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HARDBACK price:$69.95 add to cart PDF BOOK your price: $54.00 add to cart PDF CHAPTERS your price: $8.80 select Rights & Permissions Free Resources PDF SUMMARY Display this book on your site! Related Titles Human Biomonitoring for Environmental Chemicals Gulf War and Health: Volume 3. Fuels, Combustion Products, and Propellants Other Related Titles Biomarkers: Medical and Workplace Applications (1998) Joseph Henry Press (JHP) Citation Manager Export the bibliographic data for this book in your chosen format Web Search Builder Use this book's key terms to search within this book, across our collection, or across the Web. Skim This Chapter Skim this chapter and use this chapter's key terms to search within this book. Reference Finder Paste in your own text to find books that relate to your topic. Citation Manager National Research Council. "FRONT MATTER." Biomarkers: Medical and Workplace Applications. Washington, DC: The National Academies Press, 1998. 1. Print. Please select a format: Page I   E-mail  Buzz This  Facebook  Delicious  Stumble  Twitter More The following HTML text is provided to enhance online readability. Many aspects of typography translate only awkwardly to HTML. Please use the page image as the authoritative form to ensure accuracy. BIOMARKERS Medical and Workplace Applications MORTIMER L. MENDELSOHN, LAWRENCE C. MOHR, and JOHN P. PEETERS, Editors JOSEPH HENRY PRESS Washington, D.C. 1998 Page I FRONT MATTER (R1-R8) I INTRODUCTION (1-50) II PHYSICAL MEASUREMENTS (51-114) III ABERRATIONS, ADDUCTS, AND MUTATIONS (115-186) IV METABOLIC SUSCEPTIBILITY (187-254) V ORGAN-AND SYSTEM-SPECIFIC BIOMARKERS (255-334) VI CARCINOGENESIS (335-374) VII SOCIETAL ASPECTS AND CONCERNS (375-434) CONTRIBUTORS (435-440) INDEX (441-456)

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Biomarkers: Medical and Workplace Applications BIOMARKERS Medical and Workplace Applications MORTIMER L. MENDELSOHN, LAWRENCE C. MOHR, and JOHN P. PEETERS, Editors JOSEPH HENRY PRESS Washington, D.C. 1998

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Biomarkers: Medical and Workplace Applications JOSEPH HENRY PRESS 2101 Constitution Avenue, N.W. Washington, DC 20418 The Joseph Henry Press, an imprint of the National Academy Press, was created with the goal of making books on science, technology, and health more widely available to professionals and the public. Joseph Henry was one of the founders of the National Academy of Sciences and a leader of early American science. Any opinions, findings, conclusions, or recommendations expressed in this volume are those of the authors and do not necessarily reflect the views of the U.S. Departments of Energy, Health and Human Services, and Defense, or of the U.S. National Academy of Sciences. This publication was supported by grant DE-FG01-96EW56094 from the U.S. Department of Energy. Library of Congress Cataloging-in-Publication Data Biomarkers : medical and workplace applications / Mortimer L. Mendelsohn, Lawrence C. Mohr, and John P. Peeters, editors. p. cm. Includes bibliographical references and index. ISBN 0-309-06422-8 (alk. paper) 1. Biochemical markers—Congresses. I. Mendelsohn, Mortimer L. II. Mohr, Lawrence C., 1947- . III. Peeters, John P., 1958- . OH438.4.B55B55 1998 616.07—dc21 98-3882 CIP Cover Photo: Computer-generated image of DNA. Copyright Will and Deni McIntyre/Photo Researchers, Inc. Copyright 1998 by the National Academy of Sciences. All rights reserved. Printed in the United States of America.

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Biomarkers: Medical and Workplace Applications Preface Biomarkers are observable properties of an organism that can be used in four general ways: (1) to identify the organism's presence, as in microbiology or forensic pathology; (2) to estimate the organism's prior exposure, as in risk assessment; (3) to identify changes or effects occurring in the organism, as in toxicology and diagnostic medicine; and (4) to assess the underlying susceptibility of the organism, as in genetics and pharmacology. This volume is concerned with the last three applications of biomarkers as they pertain to human health, with an emphasis on the quantification of occupational or environmental exposures and the detection of genetically determined susceptibilities to the development of certain diseases. The study of human susceptibility is about to undergo a major transformation as the Human Genome Project gains momentum. Comparative sequencing of genes across the human population is already uncovering abundant DNA polymorphisms, and any given polymorphism can range from having no biological effect, to having subtle effects, to having severe life-threatening effects—all confounded by the interaction of the gene (or genes) with many others. Experts in the field of genomics predict that large-scale automated detection of such DNA changes will soon allow the routine genetic characterization of individuals using the DNA chip or other similar technologies. Thus, from a blood sample, a hair, or an exfoliated cell, one may soon be able to define a person's risk of disease, ascertain unique susceptibilities to environmental exposures, predict individual drug responses, recommend optimal diets, and prescribe preferred or prohibited life-styles and occupations. The ability to generate such intimate information about a person is, of course, a double-edge sword. Predicting likely disease can be a blessing if disease prevention is a consequence. On the other hand, if genetic testing reveals a

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Biomarkers: Medical and Workplace Applications high probability of developing a lethal or untreatable disease such as Huntington's chorea, many may prefer not to know the outcome. Similarly, evaluating occupational choices can be very helpful to the young uncommitted student but very problematic for a worker whose employer or potential employer has discovered that he or she has a significant disease susceptibility related to a routine workplace exposure or suffers from the effects of a prior chemical exposure. Governments, courts, medicine, businesses, and the general population will inevitably be faced with difficult challenges concerning the effects on people's lives of such biomarkers of susceptibility or exposure. New laws and public policy that preserve the health of individuals without threatening their personal freedom, job security, or well-being will have to be considered. These and similar issues, combined with the state of the art of biomarker research, are the subject of this volume, and of the meeting on which it is based: Biomarkers, the Genome and the Individual: Workplace and Medical Implications of a Rapidly Evolving Technology. This major international meeting was held in Charleston, South Carolina, May 4–8, 1997, and hosted by the Medical University of South Carolina under the sponsorship of the U.S. Department of Energy. The meeting and the book are sequels of an earlier biomarker meeting held in 1994 and published as Biomarkers and Occupational Health: Progress and Perspectives (1995, Joseph Henry Press, Washington D.C.). The volume begins with a historical review of the limited effectiveness of biomarkers in past applications and ends with an optimistic assessment of how new and accurate biomarkers have led rapidly to effective legislation to control two environmental toxins, lead and carbon monoxide. In between are detailed discussions of the way biomarkers are validated and used epidemiologically; a variety of powerful physical techniques for measuring and applying biomarkers; an excellent, up-to-date survey of adducts, chromosome aberrations, and mutations as biomarkers; four current examples of metabolic susceptibility; a series of organ-specific approaches to biomarkers; the role of biomarkers in carcinogenesis; and finally, summaries of the present and future status of biomarkers in occupational medicine, the courtroom, and the legislature. Several excellent literature reviews are included as well. The range and relevance of material should make this a highly useful tool for all those involved in efforts to develop and apply biomarker technologies for medical and occupational purposes. It is our belief that an informed society is essential if such technologies are to be used ethically and effectively. Every chapter of this book has been written and edited within the framework of this fundamental belief. MORTIMER L. MENDELSOHN, M.D., Ph.D. LAWRENCE C. MOHR, M.D. JOHN P. PEETERS, Ph.D.

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Biomarkers: Medical and Workplace Applications Contents I INTRODUCTION         Susceptibility Biomarkers in the Workplace: Historical Perspective Michael Gochfeld   3     Epidemiological Validation of Biomarkers of Early Biological Effect and Susceptibility Paul A. Schulte and Nathaniel Rothman   23     Finding a Biomarker Is a First Step Rogene F. Henderson   33     Practical Uses of Biomarkers in Population Studies Geoffrey R. Howe   41 II PHYSICAL MEASUREMENTS         Technical Aspects of the Electron Paramagnetic Resonance Method for Tooth Enamel Dosimetry Marc F. Desrosiers and Alexander A. Romanyukha   53     Validation of Electron Spin Resonance Studies of Tooth Enamel to Estimate Gamma-Ray Exposure in Atomic Bomb Survivors Nori Nakamura, Chuzo Miyazawa, Shozo Sawada, Mitoshi Akiyama, and Akio A. Awa   65     Measuring Bone Lead as a Biomarker of Cumulative Lead Dose Using K X-Ray Fluorescence Howard Hu, Rokho Kim, Gail Fleischaker, and Antonio Aro   71     Technologies for Measuring Recent Exposures: Volatile Chemicals and the E2R Monitor Karla D. Thrall and Donald V. Kenny   87     DNA Adducts Using Accelerator Mass Spectrometry Kenneth W. Turteltaub, Chitra Mani, Karen H. Dingley, Graham Bench, and Robert J. Mauthe   99

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Biomarkers: Medical and Workplace Applications III ABERRATIONS, ADDUCTS, AND MUTATIONS         Use of Chromosome Translocations for Measuring Prior Environmental Exposures in Humans James D. Tucker   117     Use of DNA Adducts in Biomonitoring Kari Hemminki, Vladimir Bykov, Ke Yang, and Heli Rajaniemi   133     Risk Assessment Biomarkers for Alkylating Agents and Aromatic Amines Based on a Reference Value Concept Leopold W. Miksche and Juergen Lewalter   155     Somatic Mutations as Multipurpose Biomarkers Richard J. Albertini   167 IV METABOLIC SUSCEPTIBILITY         Acetyltransferase Polymorphisms and Disease Susceptibility Christine B. Ambrosone and Fred F. Kadlubar   189     Glutathione S-Transferase Polymorphism and Susceptibility to Cancer Brian Ketterer   211     Ethnic Variation and Genetic Susceptibility: Glucose-6-Phosphate Dehydrogenase Deficiency David J. Jollow and David C. McMillan   227     Genetic Susceptibility to Tobacco-Related Lung Cancer Peter G. Shields   241 V ORGAN- AND SYSTEM-SPECIFIC BIOMARKERS         Elevated Plasma Cotinine as a Quantitative Biomarker of Tobacco Smoke Exposure Linda D. Youngman   257     The Clara Cell Protein, CC16: A Biomarker of Pulmonary Toxicity Alfred Bernard, Fabrice Broeckaert, Cédric Hermans, and Bernard Knoops   273     Beryllium Biomarkers: Application of Immunologic, Inflammatory, and Generic Tools Lee S. Newman   285     Biomarkers of Acquired Immunity as Indicators of Prior Environmental Exposures Robert F. Vogt, Jr., Wanda E. Whitfield, Richard J. Jackson, and Eric J. Sampson   301     Patterns of Tubular Proteinuria from Metals and Solvents Richard P. Wedeen, Iris Udasin, Nancy Fiedler, Patrick D'Haese, Marc E. Debroe, Emilo Gelpi, and Keith W. Jones   311

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Biomarkers: Medical and Workplace Applications     Characterizing Reproductive Risks Using Biomarkers of Reproductive Toxicity Donald R. Mattison, Sati Mazumdar, Yikang Xu, Nancy Sussman, and Vincent C. Arena   323 VI CARCINOGENESIS         Biomarkers and Mechanisms of Human Radiation Carcinogenesis Mortimer L. Mendelsohn and Donald A. Pierce   337     Mutant Oncoprotein Biomarkers in Chemical Carcinogenesis Yongliang Li, Marina Asherova, Marie-Jeanne Marion, and Paul W. Brandt-Rauf   345     Biological Markers of Aflatoxin B1 in Hepatocellular Cancer in Taiwan Regina M. Santella, Chien-Jen Chen, Yu-Jing Zhang, Ming-Whei Yu, and Li-Yu Wang   355     Biomarkers of Leukemia Risk from Benzene Martyn T. Smith and Nathaniel Rothman   365 VII SOCIETAL ASPECTS AND CONCERNS         Use of Biomarkers in Occupational Medicine Robert J. McCunney   377     Implications of Genetic Testing for Medical Examinations in the Workplace Myron C. Harrison   387     Current and Potential Applications of Genetic Biomarkers Within the Military Barry H. Thompson, Philip L. Ross Michael, A. Marino, and Philip Belgrader   397     Biomarkers in the Courtroom Franklin M. Zweig   407     Ethical Issues of Genetic Testing for Workers Eula Bingham   415     Biomarkers in Cost-Benefit Analysis and Regulatory Control: Lead, Asbestos, Carbon Monoxide, and Benzene Michael A. McMenamin and Bernard D. Goldstein   423 Contributors   435 Index   441

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