Program - Society of Toxicology

50 th Anniversary Annual Meeting and ToxExpo
Program Description (Continued)
Tuesday
Abstract # Abstract #
industries, many investigators currently use primary hepatocytes or transformed
hepatocyte-derived cell lines in lieu of animal studies. These models
have serious limitations including major differences in the expression of
xenobiotic metabolizing enzymes compared to the intact liver. There is a
clear need for the identification and characterization of biologically-relevant
in vitro models that can recapitulate the functions, cell interactions, and
responses to chemicals found in vivo. A number of exciting in vitro models
of the liver have been recently developed which make them potentially
better models for predicting responses in vivo than conventional cultures.
We will characterize the use of a number of in vitro models of the liver
including 2D and 3D co-cultures containing hepatocytes and other cell
types. Our panel of experts have an extensive experience in the characterization
and use of these models and will discuss applications of the models
including toxicity screening, metabolic activation, mode-of-action determination
using toxicogenomics and species extrapolation. This particular topic
will be useful to those interested in high-throughput screening, hepatotoxicity,
and mode-of-action research.
#1311 12:00 LIVERS ON A PLATE: NEXT GENERATION
HEPATOCYTE MODELS FOR HIGH-
THROUGHPUT SCREENING AND
MODE-OF-ACTION PREDICTION. ​C.
Corton 1 , S. Khetani 4 , L. Griffith 3 , D. Applegate 2
and S. D. Hester 1 . 1 Integrated Systems Toxicology
Division, U.S. EPA, Durham, NC, 2 RegeneMed,
Inc., San Diego, CA, 3 MIT, Cambridge, MA and
4
HepreGen Corporation, Medford, MA.
12:00 INTRODUCTION. ​Chris Corton
12:05 IN VITRO TOXICOGENOMICS AND
CHRONIC TOXICITY ASSESSMENT USING
3D LIVER CO-CULTURE. ​Dawn Applegate
12:25 PERFUSED MULTIWELL PLATE FOR 3D
LIVER TISSUE ENGINEERING. ​Linda Griffith
12:45 APPLICATIONS OF MICROSCALE ANIMAL
AND HUMAN IN VITRO LIVER MODELS IN
TOXICOLOGY. ​Salman Khetani
1:05 HEPATOCYTE MODELS FOR
PRIORITIZATION AND MODE-OF-ACTION
PREDICTION OF ENVIRONMENTALLY-
RELEVANT CHEMICALS. ​Susan Hester
Tuesday Afternoon, March 8
12:15 PM to 1:05 PM
Room 201
Distinguished Toxicology Scholar Award
Lecture: Cloning and Functional Analysis of
the Aryl Hydrocarbon Nuclear Translocator
(ARNT)
Lecturer: Oliver Hankinson, University of California,
Los Angeles, CA.
In 1991 we cloned ARNT, which we knew to be required for activity of
the Aryl Hydrocarbon Receptor (AHR). We subsequently showed that
ARNT is the obligate dimerization partner for AHR. ARNT represented
a new class of transcription factor, the basic helix-loop-helix-Per-Arnt-
Sim (bHLH-PAS) family. AHR, which was cloned the following year,
also proved to be a bHLH-PAS protein. These observations were very
surprising, since most investigators expected that AHR and its dimerization
partner would be members of the nuclear receptor superfamily.
Further studies by our group and others identified functional domains
of these proteins, and lead to a broad understanding of their roles in
transcriptional activation and chemical carcinogenesis. In 1995, Hypoxia
Inducible Factor (HIF) was cloned, and shown to be a dimer of ARNT
and another bHLH-PAS protein. Studies by us and others have shown
that ARNT is directly involved in tumor growth, angiogenesis, wound
healing, diabetes and stroke through its role as a component of HIF. Our
recent studies have focused on defining the roles of coactivator and other
facilitator proteins in the AHR/ARNT- and HIF-dependent induction of
gene transcription. Such proteins may represent nodal points for crosstalk
between these pathways and other pathways of gene regulation.
Tuesday Afternoon, March 8
12:30 NOON to 2:00 PM
Renaissance Congressional A
Regional Chapter Student Luncheon: Northeast Regional
Chapter
Tuesday Afternoon, March 8
1:00 PM to 4:30 PM
Exhibit Hall
Poster Session: Medical Devices
Chairperson(s): Lori Moilanen, 3M, St. Paul, MN.
Displayed: 1:00 PM–4:30 PM
Author Attended: 1:00 PM–2:45 PM
#1312 Poster Board Number.....................................101
EVALUATION OF THE SENSITIVITY
OF ENDPOINTS IN THE ISO 10993-11
SYSTEMIC TOXICITY STANDARD USING
POSITIVE CONTROL COMPOUNDS. ​A.
Freeman 1,2 , A. Komiyama 1 , J. Fazio 1,3 , S. Hamilla 1,4 ,
H. Dinesdurage 1 and R. P. Brown 1 . 1 U.S. FDA, Silver
Spring, MD, 2 University of Maryland, College Park,
MD, 3 Western New England College, Springfield,
MA and 4 University of Connecticut, Storrs, CT.
#1313 Poster Board Number.....................................102
RAPID TOXICITY SCREENING OF
POLYMERIC MATERIALS USING THE
MICROTOX ASSAY. ​P. Kulkarni, H. Dinesdurage
and R. P. Brown. CDRH, U.S. FDA, Silver Spring,
MD.
232
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