Trichothecene Mycotoxicosis Pathophysiologic Effects (1989): Volume II

207 Pages·2018·14.366 MB·English

by  Beasley, Val Richard

Trichothecene
Mycotoxicosis:
Pathophysiologic
Effects
Volume II
Editor
Val Richard Beasley, Ph.D.
Co-Director
National Animal Poison Control Center
Assistant Professor of Toxicology
College of Veterinary Medicine
University of Illinois
Urbana, Illinois
First published 1989 by CRC Press
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Reissued 2018 by CRC Press
© 1989 by Taylor & Francis
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INTRODUCTION
The mycotoxins, toxins produced by fungi, include compounds of widely varying chemical
structure and toxic potential. The differences among mycotoxins are similar to those of plant
toxins which also vary widely, but which contain groups of similar compounds that share
common mechanisms of action. The trichothecenes are one group of fungal metabolites that
occur widely in nature, especially as contaminants of grains and sometimes forages. Although
there is evidence that the trichothecenes share common mechanisms of action and similar target
organ/systems, differences exist, especially in potency.
The trichothecenes are cytotoxic, but many of their effects are due to secondary processes
which are set in motion sometimes by ill-defined mechanisms. This book is arranged to address
some of the known primary effects of trichothecene mycotoxins at the biochemical and whole
animal levels. It also attempts to review and discuss some of the investigations that have
addressed a range of other concerns that pertain to any naturally occurring toxicant that has the
potential to contaminate the food supply. For example, information is included on investigations
of natural occurrence and of the mutagenic and carcinogenic potential of the toxins. The results
of studies of potential preventive and therapeutic approaches are also described.
There are instances of unresolved differences of opinion, as in the case of underlying
biochemical mechanisms of action. It has been particularly challenging to interpret the diversity
of effects induced by several trichothecenes when studied in various cells, tissues, and
organisms, administered by a number of routes of administration, at different doses or
concentrations, and at dissimilar intervals. In the hope of shortening the time needed to
overcome these difficulties, the authors have sought to discuss a range of observations
delineating both areas of agreement and aspects remaining to be clarified.
The final chapter of the volumes is comprised of an effort to integrate the various observations
detailed throughout the book. With the continued efforts of not only the many dedicated
scientists who served as contributors to these volumes, but also with input from the many other
authors cited herein and those to follow, our understanding of these interesting compounds will
continue to expand. We have already learned enough to greatly reduce the adverse effects of the
trichothecene mycotoxins on humans and other animals.
THE EDITOR
Val Richard Beasley, D.V.M., Ph.D., is Co-Director of the National Animal Poison Control
Center and Assistant Professor of Toxicology, College of Veterinary Medicine, University of
Illinois, Urbana.
He received his D.V.M. from Purdue University, Lafayette, Indiana, and his Ph.D. from the
University of Illinois. Prior to his current position, Dr. Beasley was owner of Old Troy Pike
Veterinary Clinic in Dayton, Ohio and a research associate in the University of Illinois College
of Veterinary Medicine.
During his career, he has been extremely active in research, publishing, and lecturing. Over 175
publications have been authored, co-authored, or edited by Dr. Beasley, many of which in
conjunction with contributors to the present volumes. The research in which he has participated
as a principal investigator, investigator, or collaborator has received grant awards in excess of
$4.75 million. Under his instruction as a graduate advisor in the College of Veterinary Medicine,
two of his students were selected as recipients of the Joseph O. Alberts Award; one of these
students was recognized by the American Association of Physiologists and Pharmacologists for
best graduate student paper in 1987. Another of his graduate students was presented with an
award for best poster presentation at the Midwest Regional Chapter of the Society of Toxicology
in 1988. Additionally, Dr. Beasley’s expertise in the field of veterinary toxicology has been
called upon in EPA hearings and in a civil case pertaining to environmental contamination.
Among his memberships in professional societies are the American Veterinary Medicine
Association, the Illinois State Veterinary Medicine Association, Fellow of the American
Academy of Veterinary and Comparative Toxicology, and the International Association for
Aquatic Animal Medicine. He is a member of Phi Zeta and Sigma Xi and holds veterinary
licenses in four states.
To the most inspiring teacher of science in my life’s experience,
John Van Sickle of Westlane Junior High School, Indianapolis, and to my
parents and my beloved family, Victoria, Lelah, and Livia
CONTRIBUTORS
Val R. Beasley, D.V.M., Ph.D. Roseanne M. Lorenzana
Co-Director Veterinary Bioscience Department
National Animal Poison Control Center University of Illinois
Assistant Professor of Toxicology Urbana, Illinois
College of Veterinary Medicine
University of Illinois Gregg Lundeen
Urbana, Illinois Pfizer Central Research
Groton, Connecticut
James K. Bubien
Department of Physiology and Victor Fei Pang, Ph.D., D.V.M.
Biophysics Department of Pathology
University of Alabama Pig Research Institute, Taiwan
Birmingham, Alabama Chunan, Taiwan
David L. Bunner Robert H. Poppenga
Pathophysiology Department Animal Health Diagnostic Laboratory
USAMRIID College of Veterinary Medicine
Fort Detrick Michigan State University
Frederick, Maryland East Lansing, Michigan
Giora Feuerstein, M.D. H. Bruno Schiefer, Ph.D.
Department of Neurology Professor and Director
USUHS Toxicology Research Center
Bethesda, Maryland University of Saskatchewan
Saskatoon, SK, Canada
Robert Fricke
Pathophysiology Division Michael J. Taylor, Ph.D.
USAMRIID System Toxicology Branch
Fort Detrick NIH, NTP, NIEHS
Frederick, Maryland Research Triangle Park, North Carolina
Patricia A. Gentry, Ph.D. Charles Templeton
Professor Pathophysiology Division
Department of Biomedical Sciences USAMRIID
University of Guelph Fort Detrick
Guelph, ON, Canada Frederick, Maryland
W. Thomas Woods, Jr.
Department of Physiology and Biophysics
University of Alabama
Birmingham, Alabama
TABLE OF CONTENTS
Volume I
Chapter 1
The Natural Occurrence of Trichothecenes............................................................................1
Peter M. Scott
Chapter 2
Biochemical Mechanism of Action of Trichothecene Mycotoxins......................................27
Barry Feinberg and Calvin S. McLaughlin
Chapter 3
The Distribution, Metabolism, and Excretion of Trichothecene Mycotoxins......................37
S. P. Swanson and R. A. Corley
Chapter 4
Mutagenicity and Carcinogenicity of T-2 Toxin..................................................................63
W. M. Haschek
Chapter 5
Anticancer Properties of Trichothecenes...............................................................................73
Bruce B. Jarvis and Amelia M. Acierto
Chapter 6
Lethal Toxicity and Nonspecific Effects.............................................................................107
H. L. Trenholm, D. W. Friend, R. M. G. Hamilton, D. B. Prelusky, and B. C. Foster
Chapter 7
Reproductive Toxicology of Trichothecenes.......................................................................143
B. Magnus Francis
Chapter 8
Acute Respiratory Tract Toxicity of the Trichothecene Mycotoxin, T-2 Toxin................161
Donald A. Creasia and Richard J. Lambert
Index....................................................................................................................................171
Volume II
Chapter 1
The Immunotoxicity of Trichothecene Mycotoxins...............................................................1
Michael J. Taylor, Victor F. Pang, and Val R. Beasley
Chapter 2
Effects on Hemostasis and Red Cell Production..................................................................39
P. A. Gentry
Chapter 3
Effects on the Digestive System and Energy Metabolism..........................................................61
H. B. Schiefer and V. R. Beasley
Chapter 4
Effects on the Circulatory System........................................................................................91
James K. Bubien, Gregg Lundeen, Charles Templeton, and W. T. Woods, Jr.
Chapter 5
Effects of Trichothecene Mycotoxins on the Nervous System...........................................111
G. Feuerstein, R. M. Lorenzana, and V. R. Beasley
Chapter 6
Effects on the Integumentary System..................................................................................123
V. F. Pang, H. B. Schiefer, and V. R. Beasley
Chapter 7
Treatment and Prophylaxis for Trichothecene Mycotoxicosis............................................135
Robert F. Fricke and Robert H. Poppenga
Chapter 8
Conclusions and Future Directions for Research.................................................................169
Val R. Beasley, David L. Bunner, and Robert H. Poppenga
Index....................................................................................................................................191
Volume II 1
Chapter 1
THE IMMUNOTOXICITY OF TRICHOTHECENE MYCOTOXINS
Michael J. Taylor, Victor F. Pang, and Val R. Beasley
TABLE OF CONTENTS
I. Introduction..................................................................................................................2
A. Alimentary ToxicA leukia and Its ImmunotoxicN ature..................................2
B. Immune System...............................................................................................2
II. Immunotoxic Effects...................................................................................................5
A. Immune-Related Dermal Responses to Trichothecene
Mycotoxins.......................................................................................................5
B. Trichothecene-InducedI mmunodysfunction in Man........................................9
III. Animal Models...........................................................................................................9
A. Monkey.........................................................................................................20
B. Cat.................................................................................................................20
C. Swine.............................................................................................................20
D. Cattle..............................................................................................................23
E. Sheep..............................................................................................................23
F. Guinea Pig.....................................................................................................24
G. Rabbit.............................................................................................................24
H. Rat.................................................................................................................24
I. Mouse.............................................................................................................25
1. Immunopathology...............................................................................25
2. Lymphocyte Proliferation.................................................................27
3. Antibody Production..........................................................................27
4. Delayed-Type Hypersensitivity.........................................................28
5. Graft Rejection.................................................................................29
6. Adoptive Transfer..............................................................................29
7. In Vitro Cellular Reconstitution Experiments.................................29
8. Resistance to Infection......................................................................30
J. Poultry...........................................................................................................30
IV. Antitrichothecene Mycotoxin Antibodies..................................................................31
V. Proposed Mechanisms of Immunotoxicity.................................................................32
VI. Conclusion..................................................................................................................33
References.............................................................................................................................33