Non-linear Dose-Response Relationships in Biology, Toxicology and Medicine, Amherst, Massachusetts, May 28-30, 2003

A. NAME AND LOCATION
Non-linear Dose-Response Relationships in Biology, Toxicology and Medicine
Amherst, Massachusetts
May 28-30, 2003

B. SPONSORS
SAMUELI INSTITUTE
Department of Energy
Food and Drug Administration
Health Canada
Others

C. PURPOSE AND FOCUS
To discuss the significance of biological effects of low level exposures. Knowledge of low dose effects is becoming a driving force in the field of risk assessment and chemotherapeutics. The conference provides the most current advances in the area of dose response with respect to chemical and radiation induced stresses and a host of effects of pharmaceutical agents that have profound biomedical implications.

D. AUDIENCE
Basic and clinical scientists, public health providers, government researchers and policy makers.

E. OUTCOME
Individually selected papers presented at the conference were published in a Samueli Institute Proceedings in May 2004.


TABLE OF CONTENTS

FOREWORD FROM THE ORGANIZERS   v
Edward J. Calabrese and Wayne B. Jonas

EDITOR’S COMMENTS   vi
Ronald A. Chez and John A. Ives
CONTRIBUTING AUTHORS  vii
CONTRIBUTED MANUSCRIPTS

PRACTICAL IMPLICATIONS OF NON-LINEAR  1

EFFECTS IN RISK ASSESSMENT HARMONIZATION
John A. Bukowski, R. Jeffrey Lewis

DOSE-RESPONSE CURVES IN CHEMICAL CARCINOGENESIS   9
William J. Waddell

DETOXICATION STRATEGY OF EPOXIDE HYDROLASE—   19
THE BASIS FOR A NOVEL THRESHOLD FOR DEFINABLEWe will
GENOTOXIC CARCINOGENS
Franz Oesch, Jan Gerog Hengstler., Michael Arand

EVALUATION OF THE EXPOSURE-RESPONSE RELATIONSHIP   26
OF LUNG CANCER MORTALITY AND OCCUPATIONAL EXPOSURE
TO HEXAVALENT CHROMIUM BASED ON PUBLISHED
EPIDEMIOLOGICAL DATA
Edwin van Wijngaarden, Kenneth A. Mundt, Rose S. Luippold.

THE USE OF STREPTOLYSIN O FOR THE TREATMENT OF  35
SCARS, ADHESIONS AND FIBROSIS: INITIAL INVESTIGATIONS
USING MURINE MODELS OF SCLERODERMA
Stephen S. Mamber, Vit Long, Ryan G. Rhodes, Sunthorn Pond-Tor,
Lyn R. Wheeler, Kellie Fredericks, Brian VanScoy, Jean-Frederic Sauniere,
John McMichael, Remy Steinschneider, Jean-Claude Laurent

U-SHAPED DOSE-RESPONSE FUNCTION BETWEEN   52
DEYDROEPIANDRO-TERONE SULFATE (DHEAS)
AND MEMORY RELATED PROCESSING BY THE
HIPPOCAMPUS
David M. Diamond

METALLOTHIONEIN AS AN ADAPTIVE PROTEIN 60
PREVENTS DIABETES AND ITS TOXICITY
Lu Cai

MOLECULAR MECANISMS OF ANTI-AGING HORMETIC EFFECTS  77
OF MILD HEAT STRESS ON HUMAN CELLS
Suresh I.S. Rattan, Yvonne E.G. Eskildsen-Helmond, Rasmus Beedholm

DOSE RESPONSE RELATIONSHIPS IN EXPRESSION OF BIOMARKERS  89
OF CELL PROLIFERATION IN IN VITRO ASSAYS AND
INHALATION EXPERIMENTS
Brooke T. Mossman, Arti Shukla, Pamela Vaceck

MECHANISTIC MODEL PREDICTS LOW-DOSE NON-LINEARITY  101
OF LIVER TUMOR RISK IN MICE FED FUMONISIN B1
Ralph L. Kodell., Angelo Turturro

RESPONSES OF CULTURED ASTROCYTES, C6 GLIOMA AND  110
1321NI ASTROCYTOMA CELLS TO AMYLOID-PEPTIDE FRAGMENTS
V.W. Pentreath, C. Mead

EFFECTS OF LOW AND VERY LOW DOSE OF SIMPLE   130
PHENOLICS ON PLANT PEROXIDASE ACTIVITY
Ezbiea Malarczyk, Janina Kochmanska-Rdest, MarzannaPazdzioch-Czochra

 

CONTRIBUTING AUTHORS

Michael Arand, Prof. Dr.
Institut für Pharmakologie und Toxikologie
der Universitat
Versbacher Str. 9
D-97078 Wurzburg
Germany

arand@toxi.uni-wuerzburg.de
John A. Bukowski
ExxonMobil Biomedical Sciences, Inc.
1545 Route 22 East, Room LF278
Annandale, NJ 08801
john.a.bukowski@exxonmobil.com

Lu Cai, M.D., Ph.D.
511 South Floyd Street, MDR 533
Department of Medicine
University of Louisville School of Medicine
Louisville, KY 40202
L0cai1001@louisville.edu

Edward J. Calabrese, Ph.D.
School of Public Health
Environmental Health Sciences
Morrill I, N344
University of Massachusetts
Amherst MA 01003
edwardc@schoolph.umass.edu

Ronald A. Chez, M.D.
Samueli Institute for Informational Biology
2101 E. Coast Highway
Suite 300
Corona del Mar, CA 92625
rchez@siib.org

David M. Diamond, Ph.D.
Depts. of Psychology and Pharmacology
University of South Florida
4202 E. Fowler Ave (PCD 4118G)
Tampa, FL 33620
ddiamond@chuma1.cas.usf.edu

Jan Geog Hengstler, Prof. Dr.
Universitat Leipzig
Rudolf-Bohem Institut für Pharmakologie
und Toxikologie
Härtelstr. 16-18
D-04107 Leipzig
Germany
jan.hengstler@medizin.uni-leipzig.de

John A. Ives, Ph.D.
Samueli Institute for Informational Biology
1700 Diagonal Road, Suite 400
Alexandria, VA 22314
jives@siib.org

Wayne B. Jonas, M.D.
Samueli Institute for Informational Biology
1700 Diagonal Road, Suite 400
Alexandria, VA 22314
wjonas@siib.org

Ralph L. Kodell, PhD.
Division of Biometry and Risk Assessment
National Center for Toxicological Research
3900 NCTR Road
Jefferson AR 72079
rkodell@nctr.fda.gov

R. Jeffrey Lewis
ExxonMobil Biomedical Sciences, Inc.
1545 Route 22 East, Room LF264
Annandale, NJ 08801
r.jeffrey.lewis@exxonmobil.com

Rose S. Luippold, M.S.
P.O. Box 2424
Amherst, MA 01004-2424
rluippold@appliedepidemiology.com

Elzbieta Malarczyk Ph.D.
Biochemistry Department
M. Curie-Sklodowska University
M. Curie-Sklodowska squer, 3
Pl-20-031 Lublin, Poland
malar@hermes.umcs.lublin.pl

Stephen W. Mamber, Ph.D.
Milkhaus Laboratory, Inc.
70 Elm Street
Providence, RI 02903
smamber@milkhaus.com

Brook T. Mossman, Ph.D.
Department of Pathology
University of Vermont, College of Medicine
89 Beaumont Ave
HSRF 218
Burlington VT 05405
brook.mossman@uvm.edu

Kenneth A. Mundt, Ph.D.
P.O. Box 2424
Amherst, MA 01004-2424
kmundt@appliedepidemiology.com

Franz Oesch, Prof. Dr.
Institute of Toxicology
University of Mainz
Obere Zahlbacher Str. 67
D-55131 Mainz
Germany
Oesch@mail.uni-mainz.de

Marzanna Pazdzioch-Czochra Ph.D.
Biochemistry Department
M. Curie-Sklodowska University
M. Curie-Sklodowska squer, 3
PL-20-031 Lublin
Poland
mpazdzio@biotop.umcs.lublin.pl

Victor W. Pentreath, B.Sc., Ph.D.
Division of Biosciences
University of Salford
Salford MS 4Wt
United Kingdom
V.W.Pentreath@salford.ac.uk

Suresh I.S. Rattan, Ph.D., D.Sc.
Department of Molecular Biology
University of Aarhus
Gustav Weids vej 10c
DK-8000 Aarhus-C
Denmark
rattan@imsb.au.dk

Angelo Turturro, Ph.D.
Division of Biometry and Risk Assessment
National Center for Toxicological Research
3900 NCTR Road
Jefferson, AR 72079
Aturturro@nctr.fda.gov

William J. Waddell, M.D.
14300 Rose Wycombe Lane
Prospect, KY 40059
bwaddell@louisville.edu

Edwin van Wijngaarden, Ph.D.
P.O. Box 2424
Amherst, MA 01004-2424
edwin1@alumni.unc.edu