Advances in Mercury Toxicology

Transcription

1 Advances in Mercury Toxicology

2 ROCHESTER SERIES ON ENVIRONMENTAL TOXICITY Series Editors: Thomas W. Clarkson and Morton W. Miller ADVANCES IN MERCURY TOXICOLOGY Edited by Tsuguyoshi Suzuki, Nobumasa Imura, and Thomas W. Clarkson BIOLOGICAL MONITORING OF TOXIC METALS Edited by Thomas W. Clarkson, Lars Friberg, Gunnar F. Nordberg, and Polly R. Sager THE CYTOSKELETON: A Target for Toxic Agents Edited by Thomas W. Clarkson, Polly R. Sager, and Tore L. M. Syversen REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY OF METALS Edited by Thomas W. Clarkson, Gunnar F. Nordberg, and Polly R. Sager 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.

3 Advances in Mercury Toxicology Edited by Tsuguyoshi Suzuki University of Tokyo Tokyo, Japan Nobumasa Imura Kitasoto University Tokyo, Japan and Thomas W. Clarkson University of Rochester School of Medicine Rochester, New York Springer Science+Business Media, LLC

4 Library of Congress Catalog1ng-1n-PublIcatlon Data Advances in mercury toxicology / edited by Tsuguyoshi Suzuki, Nobumasa Imu^a, and Thomas W. Clarkson. p. cm. (Rochester series on environmental toxicity) "Proceedings of a Rochester International Conference in Environmental Toxicity, held August 1-3, 1990 in Tokyo, Japan" T.p. verso. Includes bibliographical references and index. 1. Mercury Toxicology Congresses. I. Suzuki, Tsuguyoshi, II. Imura, Nobumasa, III. Clarkson, Thomas W. IV. Rochester International Conference on Environmental Toxicity (19th Tokyo, Japan) V. Series. [DNLM: 1. Environmental Pollutants adverse effects congresses. 2. Mercury Poisoning congresses. QV 293 A244] RA1231.M5A '25 dc20 DNLM/DLC for Library of Congress CIP Proceedings of a Rochester International Conference in Environmental Toxicity, held August 1-3, 1990, in Tokyo, Japan ISBN DOI / ISBN (ebook) Springer Science+Business Media New York 1991 Originally published by Plenum Press, New York in 1991 Softcover reprint of the hardcover 1st edition 1991 All rights reserved No part of this book may be reproduced, stored in a rëtrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher

5 Conference Coordinators Seiichiro Himeno Kitasato University Tokyo, Japan and Michael A. Terry University of Rochester School of Medicine Rochester, New York Sponsored by Japan Society for the Promotion of Science Inoue Foundation for Science University of Tokyo National Science Foundation (INT ) leoh Subcommittee of Toxicology of Metals v

6 We gratefully acknowledge additional support from the following contributors: Banyu Pharmaceutical Company, Ltd. Chugai Pharmaceutical Company, Ltd. Eisai Company, Ltd. Japan Immunoresearch Laboratories Japan Industrial Safety and Health Association Kanebo Ltd. Kato Shinobu Meiji Seika Kaisha, Ltd. Mitsui Pharmaceuticals Inc. Nihon Millipore Ltd. Nippon Instruments Corp. Nippon Kayaku Company, Ltd. Nippon Roussel K.K. Nitto Boseki Company, Ltd. Sankyo Company, Ltd. San sou Seisakusho K.K. Sapporo Breweries Ltd. Schering-Plough K.K. Sugiyama-Gen Iriki Company, Ltd. Taiho Pharmaceutical Company, Ltd. Terumo Corporation Varian Instruments Ltd. Yamamura Yukio Yamanouchi Pharmaceutical Company, Ltd. vi

7 DEDICATION Tsuguyoshi Suzuki was born in Tokyo on 26 February, He graduated from the Faculty of Medicine at the University of Tokyo in He completed his doctor's course in the Division of Medical Sciences in the Graduate School of the University of Tokyo in His professional career started with his appointment as Instructor in the Department of Public Health, Faculty of Medicine, University of Tokyo in Subsequently, in the same department, he rose to the position of Assistant Professor in 1966 and to Associate Professor in In 1971, he assumed the post of Professor of the Department of Public Health in the School of Medicine in the University of Tohoku, a position which he held until 1979 when he returned to the University of Tokyo as Professor of Human Ecology in the Faculty of Medicine. In addition to holding this professorship, Dr. Suzuki served as director of the Graduate Course in the School of Health Sciences, Division of the Medical Science from 1984 to 1989 and became Director of the Undergraduate Course in the same School from 1989 to He has received numerous honors and acknowledgements of his scientific achievements and professional stature. These include election to the vice presidency of the Asia-Pacific Academic Consortium for Public Health from 1988 to 1989, his appointment to editorship of scientific journals including the Asia-Pacific Journal of Public Health, Nutrition Research and the Journal of Applied Toxicology. He has served on many prestigious national and international committees as well as acting as an expert advisor to the World Health Organization on public health issues. His outstanding scientific reputation in public health and toxicology is built upon over 200 publications in peer reviewed scientific journals. He introduced the concept of human ecology into understanding how human populations respond to toxic agents in their environment. His article in this book describes his latest study comparing an industrialized to a non-industrialized population's response to the toxic stress from mercury. Throughout his career interest in human populations, he established a laboratory second to none in the application of analytical techniques to human biological monitoring. Biological monitoring focussed mainly on two elements, mercury and selenium as these elements played a central role in his studies in human ecology. In the case of mercury and its compounds, he pioneered human biological monitoring with applications to a wide variety of media including historical specimens, nails, hair, milk, placenta and autopsy tissues. His human studies were complemented by highly productive experimental studies. A great deal of what we know today on the disposition of mercury vapor and methylmercury and their interaction with selenium is due to his experimental work. This unique combination of human and laboratory based research has made him a preeminent international authority on the toxicology of mercury. vii

8 Dedication Besides his great contribution to scientific progress, Dr. Suzuki has devoted himself to education of graduate and undergraduate students throughout his professional career. The unanimous opinion of the students whom he supervised is that Professor Suzuki is a severe but always encouraging teacher. His ingenuity and excellence as a teacher have been clearly proven by the fact that many of his students are now leading scientists not only in human ecology and toxicology, but also in other fields of environmental health sciences. It was therefore appropriate that this conference on Advances in Mercury Toxicology was held at Professor Suzuki's home University of Tokyo. The conference and this book is an acknowledgement from the participants, authors and co-editors of his scientific accomplishments and his outstanding international scientific reputation. viii

9 PREFACE This book is based on an international meeting organized by the University of Tokyo and the University of Rochester, and is published as one belonging to the series of Rochester International Conferences in Environmental Toxicity. The meeting on "Advances in Mercury Toxicology" was held at the University of Tokyo on August 1 to 3, The invited papers are published in this book along with an "Overview" chapter that was written by the editors at a meeting held at the University of Rochester on August 1 to 2, The purpose of the meeting was to assemble leading scientists to discuss their most recent findings on the toxicology of mercury. The time was opportune. Considerable progress has been made on the environmental fate and toxicology of mercury. Recent findings have given new insight into the global model for mercury. Transport in the atmosphere extends great distances resulting in pollution of lakes and rivers far distant from the source of mercury release. The process of methylation leads to accumulation of methylmercury in fish and thus in the human diet. New evidence indicates that acid rain and the impoundment of water for hydroelectric purposes affects the methylation and bioaccumulation processes resulting in higher levels of methylmercury in fish. Studies on the disposition of mercury in the body are now moving from the descriptive phase to one of understanding the underlying mechanisms of transport and biotransformation. New hypotheses have been proposed on mechanisms of toxicity both with regard to the central nervous system and the kidney. Understanding may be at hand why the prenatal stage of the developing brain is more susceptible to methylmercury than the mature brain. Soon we may be in a position to identify the target molecules, at least for some forms of mercury poisoning. Mechanisms of tolerance to mercury are also of considerable current interest. Included in this area is a consideration of the human ecology of mercury. Thus the meeting offered an opportunity to evaluate these new developments and to open up new avenues of research. This book reflects not only the scientific material presented at the meeting but also, through the overview section, a general evaluation of the state of knowledge of mercury toxicology at time of increasing interest in this metal. The editors wish to acknowledge the assistance to the planning and organization of this conference willingly and enthusiastically given by the staff and students of the Department of Human Ecology, Faculty of Medicine, University of Tokyo, and the Department of Public Health, School of Pharmaceutical Sciences, Kitasato University. We also thank Muriel ix

10 Preface Klein, Joyce Morgan and Kathleen Amico for their skilled and tireless help in the preparation of this book. T. Suzuki N.Imura T. Clarkson x

11 CONTENTS Overview.... T. Suzuki, N. Imura and T. W. Clarkson SESSION 1: FATE IN THE ENVIRONMENT Increased Methylmercury Contamination in Fish in Newly Formed Freshwater Reservoirs R.E Hecky, DJ. Ramsey, R.A. Bodaly, and N.E. Strange Abstract Introduction Temporal and spatial surveys on the Churchill River diversion Mesocosm studies Studies of the methylation-demethylation balance Conclusion Speciation of Mercury in the Environment H. Akagi and H. Nishimura Abstract Introduction Analytical method for total mercury Apparatus Sample digestion procedure Analytical methods for methylmercury Pretreatment and extraction Clean-up procedure Re-extraction procedure Conclusion Acknowledgements References SESSION 2: DISPOSITION IN THE BODY Individual Difference of Methylmercury Metabolism in Animals and Its Significance in Methylmercury Toxicity R.Doi Abstract Introduction xi

12 Contents Heredity of strain difference in blood mercury level Biochemical and biological behavior of methylmercury Other factors for the strain difference of MeHg metabolism Conclusion References Mechanisms of Urinary Excretion of Methylmercury(MM) p. 1. Kostyniak Abstract Introduction Strain differences in excretion rate The role of endogenous thiols Conclusion Acknowledgement References Role of Glutathione in Mercury Disposition A. Naganuma, T. Tanaka, T. Urano, and N. [mura Abstract Introduction Role of ash in biliary secretion of methylmercury Role of ash in renal uptake of methylmercury References Mechanism for Renal Handling of Methylmercury K. Hirayama, A. Yasutake and T. Adachi Abstract Introduction Transfer of MeHg to the kidney Renal uptake of MeHg Renal excretion of MeHg Conclusion References Methods for Decreasing 203Hg Retention in Relation to Age and Route of Exposure B. Kargacin and K. Kostial Abstract Introduction xii

13 Contents Materials and Methods Animals Radionuclide administration Chelation therapy Radioactivity determination Results Discussion... Conclusions Acknowledgement References Immunohistochemical Localization of Metallothionein in Organs of Rats Treated with either Cadmium, Inorganic or Organic Mercurials C. Tohyama, A. Ghaffar, A. Nakano, N. Nishimura, and H. Nishimura Abstract Introduction Materials and Methods Reagents Animal treatment Immunohistochemical staining Concentrations of metallothionein and heavy metals in the kidneys and brain Results Immunohistochemical localization of metallothionein Metallothionein localization in the rat kidney Metallothionein localization in the rat brain Discussion Acknowledgement References SESSION 3: BIOTRANSFORMATION Mercury Vapor Uptake and Oxidoreductases in Erythrocytes S. Halbach Abstract Introduction Methods Results and discussion Characteristics of the cellular uptake in a closed-exposure system for Hg-vapor The evidence for the interaction between catalase-compound-i and Hg vapor... '" Inhibition of GSH-dependent hydrogen peroxide removal Conclusions Acknowledgement References xiii

14 Contents Differential Detennination of Ionizable and Unionizable (Inert) Fonns ofinorganic Mercury in Animal Tissues H. Takahashi, K. Suetomi, and T. Konishi Abstract Introduction Methods Results and Discussion Conclusion References SESSION 4: MOLECULAR MECHANISMS OF TOXICITY Role of Neuronal Ion Channels in Mercury Intoxication T. Narahashi, O. Arakawa, and M. Nakahiro Abstract Introduction Historical review Effects on neuromuscular transmission Effects on nerve membranes Effects on neurotransmitter-activated ion channels Discussion Acknowledgements References Role of Oxidative Injury in the Pathogenesis of Methylmercury Neurotoxicity M.A. Verity and T. Sarafian Abstract... " Introduction Studies of MeHg induced neurotoxicity using cerebellar granule cells in suspension Studies in cerebellar granule cell culture and glial culture Conclusion References Alterations in Gene Expression Due to Methylmercury in Central and Peripheral Nervous Tissues of the Rat S. Omata, Y. Terui, H. Kasama, T.lchimura, T. Horigome, and H. Sugano Abstract Introduction Materials and Methods Chemicals xiv

15 Contents Animal treatment Preparation and translation of poly (A)+ mrna Sample preparation for electrophoresis Two-dimensional electrophoresis and fluorography Extraction of protein spots and counting..., Results Analysis by two-dimensional electrophoresis Calculations Changes in the synthesis of individual protein species A ~ s i g of n mthe e protein n t spots to the known protein species DIScussIon Acknowledgement References Microtubules: A Susceptible Target of Methylmercury Cytotoxicity K. Miura and N. Imura Abstract Introduction Effect of MM and inorganic mercury on macromolecule biosyntheses in mouse glioma and neuroblastoma cells Growth inhibition and microtubules disruption by MM in mouse glion1a cells Effect of microtubule disruption by MM on tubulin synthesis References DNA Damage by Mercury Compounds: An Overview M. Costa, N.T. Christie, O. Cantoni, J.T. Ze/ikoff, X.w. Wang, and T.G.Rossman Abstract Introduction Materials and Methods Results DNA damage induced by mercury compounds Oxygen radical production by HgCI The effect of mercury chloride on repair of DNA damage..., Binding of mercury to DNA Comparison of mercury chloride and methylmercury-induced DNA damage in fibroblasts and nerve cells Discussion References xv

16 Contents SESSION 5: SELENIUM AS A MODIFYING FACTOR OF MERCURY TOXICITY Possible Mechanism of Detoxifying Effect of Selenium on the Toxicity of Mercury Compounds N. [mura and A. Naganuma Abstract Introduction Changes in tissue distribution of mercury and selenium by their simultaneous administration Factors necessary for complex formation in the blood Behavior of mercury and selenium in the liver Interaction of selenium with methylmercury Interaction of selenium with metals other than mercury References Overview on the Protection Given by Selenium Against Mercurials L. Magos Abstract Introduction Selenium against sublimate intoxication Selenium against methylmercury intoxication Selenium in food versus selenite Loss of selenium through exhalation Conclusion References SESSION 6: TOXIC EFFECTS OF MERCURY Effect of Mercuric Chloride on Angiotensin II-Induced Ca ++ Transient in the Proximal Tubule of Rats H. Endou and K.Y. lung Abstract Introduction Relationship between cellular ATP and cytosolic free calcium Effect of angiotensin II on [Ca++h in isolated rat early proximal tubule Effect of mercuric chloride on [Ca++]j in rat Sl Effect of mercuric chloride on angiotensin II-induced Ca++ transient Conclusion xvi

17 Contents Acknowledgements References Effects of Methylmercury on the Developing Brain R.H. ehoi Abstract Introduction Effects of methylmercury on neuronal migration Effects of methylmercury on neuroepithelial germinal cells in ventricular zone of telencephalon of embryonic mice Effects of Methylmercury on cell-ta-cell intercictions in the developing brain Studies using rotation-mediated aggregation cultures of embryonic brain cells Effects of MeHg on neural cell adhesion molecule... '" MeHg effects on developing astrocytes MeHg effects on the membranes of astrocytes in culture Alterations in surface charge... '" Effects of meso-2,3-dimercaptosuccinic acid (DMSA) Effects of MeHg on membrane fluidity..." MeHg effects on nucleosomes of mouse fetal astrocytes MeHg effects on L-glutamate uptake in cultured astrocytes Effects of methylmercury on excitatory amino acid receptors Hydrocephalus following prenatal methylmercury poisoning Methylmercury effects on endothelial cells and perivascular astroglia of neonatal cerebellum E f f ~?f.methylmercury c t s on the interplay between proteases and protease InhIbItors Conclusion... '" 333 Acknowledgements References Experimental Approaches to Developmental Toxicity of Methylmercury M.lnouye Abstract.... " Introduction Conclusion... References Neuropathology of Methylmercury Intoxication T. Sato and Y. Nakamura Abstract Introduction Acknowledgements xvii

18 Contents References Behavioral Toxicology of Mercury Compounds H. Satoh Abstract Introduction Acknowledgement References Effect of Methylmercury on Sleep Patterns in the Rat H. Arito and M. Takahashi Abstract Introduction Methods Animals MCC administration Experiment Electrode implantation Polygraphic recording and classification of vigilance states Experiment Implantation of thermistors and ECG electrode Measurement of heart rate and body temperature Experiment 3..., Analysis of brain monoamines and their metabolites Determinations of total mercury in the brain Results Sleep-wakefulness patterns Heart rate and boy temperature Brain monoamines and their metabolites Mercl:lry concentrations in the frontal cortex Discussion..., References Effect of Inorganic Mercury on the Immune System P. Druet Abstract Introduction Mercury-induced autoimmunity or hypersensitivity reactions in humans Autoimmune glomerulonephritis Systemic angeitis Oral manifestations Immunological abnormalities associated with mercury exposure xviii

19 Contents Effect of inorganic mercury on lymphocyte functions in experimental animals Induction of hypersensitivity reactions and autoimmunity in experimental animals Guinea-pig Rat Description of the disease Effect of other inorganic mercurials, of the route of administration and of the dose Genetic control of susceptibility...,..., " Mechanisms of induction Regulation of HgClrinduced autoimmunity Mouse Rabbit Induction of immunosuppression in the rat Conclusion References SESSION 7: CLINICAL AND EPIDEMIOLOGICAL ASPECTS Exposure to Mercury in the Population S. Skerfving Abstract Introduction Biological indices of exposure Mercury levels in blood and urine Mobilization of mercury...".., Methylmercury exposure via fish Exposure to mercury through amalgam... Occupational exposure to elemental mercury vapour Effects of exposure to elemental mercury vapour Central nervous system Kidneys Endocrine organs Acknowledgements References Blood and Urinary Mercury Levels as Indicators of Exposure to Mercury Vapor Y. Yamamura, M. Yoshida and S. Yamamura Abstract Introduction...,. 427 Analytical Methods Results xix

20 Contents Elimination kinetics Mercury concentration in blood and urine of workers exposed to mercury vapor Biological monitoring of exposure Relationship between degree of exposure and elemental and inorganic.. mercury in urine DIscussIon Conclusion References Epidemiological and Clinical Features of Minamata Disease A. [gata Abstract Introduction Quantitative diagnostic procedure Epidemiological information Identification of each symptom Peripheral neuropathy Cerebellar ataxia Tremor Gait Mental deterioration Ophthalmological and otological symptoms Clinical Course Other neurological signs and symptoms Diagnostic criteria of Minamata disease Involvement of other organs Congenital Minamata disease Discussion and Conclusion References SPECIAL LECTURE AND CLOSING REMARKS Mercury in Human Ecology T. Suzuki Abstract In troduction Mercury in a tropical human ecosystem with traditional way of living in lowland Papua, New Guinea Mercury levels and ratio of inorganic to total mercury in the Gidra foods Characterization of the Gidra food with carbon and nitrogen stable isotope ratios Mercury and coexisting elements in the Gidra foods xx

21 Contents Hair mercury concentrations in the Gidra Mercury concentration in organs of contemporary Japanese and its correlation with selenium concentrations Mercury concentration in organs Selenium-mercury relationships in organs A speculative model regarding the role of selenium in adaptability to mercury Acknowledgement References APPENDIX I. Program APPENDIX II. Publications from Rochester International Conferences in Environmental Toxicity