Annual Meeting Program - Society of Toxicology

Society of Toxicology 2008
Program Description (Continued)
Abstract #
Monday Afternoon, March 17
1:30 PM to 4:15 PM
Room 6B
SYMPOSIUM SESSION: DRUG-INDUCED MITOCHONDRIAL
TOXICITY: NOVEL INSIGHTS–NOVEL TOOLS
Chairperson(s): Yvonne Will, Pfizer, Inc., San Diego, CA and Urs
Boelsterli, University of Connecticut School of Pharmacy, Storrs, CT.
Endorsed by:
Drug Discovery Toxicology Specialty Section
Mechanisms Specialty Section*
Mitochondria have been increasingly recognized as a target of drug toxicity
resulting in disruption of bioenergetics and causing oxidant stress in sensitive
organs including CNS, heart, and skeletal muscle. In addition, there is
increasing awareness that mitochondria are key mediators of drug toxicity
in a number of other organs including liver and kidney, often causing
mitochondrial outer membrane permeabilization and release of cell death
proteins. Furthermore, certain underlying disease states like diabetes, infections,
or neurodegenerative diseases can greatly alter mitochondrial function
and make the mitochondria more vulnerable to drug toxicity. Conventional
in vitro approaches in drug discovery and development have often failed to
detect mitochondrial dysfunction, and there are few animal models which
would readily reveal mitochondrial liability. This symposium will focus on
new approaches to detect, understand, and predict mitochondrial toxicity.
These novel approaches include transcriptional fingerprinting of mitochondrial
changes, transgenic mouse models, and novel in vitro tools.
#556 1:30 DRUG-INDUCED MITOCHONDRIAL
TOXICITY: NOVEL INSIGHTS–NOVEL
TOOLS. Y. Will 1 and U. A. Boelsterli 2 . 1 Drug Safety
Research and Development, Pfizer, San Diego,
CA and 2 Department of Pharmaceutical Science,
University of Connecticut, Storrs, CT.
#557 1:45 TRANSCRIPTIONAL SIGNATURE OF
MITOCHONDRIAL TOXICITIES. K. B.
Wallace. Biochemistry & Molecular Biology,
University of Minnesota Medical School, Duluth,
MN.
#558 2:15 MITOCHONDRIA IN DRUG-INDUCED
LIVER INJURY (DILI). U. A. Boelsterli.
Pharmaceutical Sciences, University of Connecticut,
Storrs, CT.
#559 2:45 INHIBITION OF ETHANOL EFFECTS BY
MITOCHONDRIAL THIOREDOXIN-2. J.
Hansen. School of Medicine, Emory University,
Atlanta, GA. Sponsor: Y. Will.
#560 3:15 LINKING MITOCHONDRIAL
DYSFUNCTION TO HYPERGLYCEMIA:
IMPACT OF MITOCHONDRIAL FIDELITY
AND OXIDATIVE STRESS ON DIABETES
AND ITS COMPLICATIONS. C. M. Palmeira.
IMAR, Mitochondrial Research Group, Department
of Zoology, University of Coimbra, Coimbra,
Portugal.
#561 3:45 STRATEGIES TO REDUCE NCE ATTRITION
DUE TO MITOCHONDRIAL TOXICITY-
DESIGNING NOVEL SCREENING
METHODS. Y. Will. Drug Safety Research and
Development, Pfizer, San Diego, CA.
Abstract #
Monday Afternoon, March 17
1:30 PM to 4:15 PM
Room 6E
Developmental Basis of Disease
SYMPOSIUM SESSION: ENVIRONMENTAL INFLUENCE ON
FEMALE PUBERTY AND BREAST TUMORIGENESIS
Chairperson(s): Elizabeth Maull, NIEHS, Research Triangle Park,
NC and Coral Lamartiniere, University of Alabama at Birmingham,
Birmingham, AL.
Endorsed by:
Carcinogenesis Specialty Section
Mechanisms Specialty Section
Molecular Biology Specialty Section*
Reproductive and Developmental Toxicology Specialty Section
Breast cancer is a complex disease, resulting from both genetic and environmental
influences. Environmental exposures during critical windows
of mammary gland development may be responsible for altering tissue
susceptibility resulting in increased risk of future breast cancer. The pubertal
hypothesis suggests that exogenous agents such as endocrine disrupting
chemicals or other dietary factors, may mimic estrogen or influence their
levels, such that the period of rapid development of the mammary gland is
extended, putting the gland at higher risk for a transition to carcinogenesis.
The NIEHS and NCI established the Breast Cancer and the Environment
Research Centers (BCERC) Network, a unique multidisciplinary, translational
grant program that includes basic biology, epidemiology, and
community outreach and translation components to address the pubertal
hypothesis. A primary objective of the BCERC Network is to explore the
influence of a select set of exposures and activities on the onset of breast
development and progression through puberty, early onset of puberty being
among the most reliable risk factors for future beast cancer. Research within
the Network spans a spectrum of biological organization: molecular mechanisms
controlling regulation of differentiation of gland stem cells; insights
into genomic and proteomic pre-disposition for disease; the impact of environmental
exposures (including diet and obesity) at sensitive windows of
development on gland development and the future risk of developing breast
cancer as well as a cohort study of puberty designed to look at both environmental
and genetic factors, and when possible their interactions, evaluating
the impact of environmental exposures (broadly defined to include dietary,
endocrine disruptors, consumer product use and socioeconomic factors) on
progression to and through puberty in young girls. The aim of this symposium
is to present the latest findings relating early environmental exposures
with alterations in pubertal milestones that predispose towards breast cancer.
#562 1:30 ENVIRONMENTAL INFLUENCE ON
FEMALE PUBERTY AND BREAST
TUMORIGENESIS. E. A. Maull 1 , S. Lynch 2 ,
D. Winn 2 , G. Collman 1 and L. Reinlib 1 . 1 National
Institute of Environmental Health Sciences, RTP, NC
and 2 National Cancer Institute, Rockville, MD.
#563 1:45 THE EFFECT OF ENVIRONMENTAL
EXPOSURES ON MAMMARY STEM CELLS
DURING PUBERTY. M. Barcellos-Hoff 1 , I.
Illa-Bochaca 1 , C. Lamartiniere 2 and Z. Werb 3 .
1
Lawrence Berkeley National Laboratory, Berkeley,
CA, 2 University of Alabama, Birmingham, AL
and 3 University of California, San Francisco, San
Francisco, CA.
#564 2:15 PRENATAL EXPOSURE TO BISPHENOL A
(BPA) INDUCES GENOMIC ALTERATIONS
IN THE RAT MAMMARY GLAND. J. Russo 1 ,
J. Pereira 1 , R. Moral 1 , C. Lamartiniere 2 and I. H.
Russo 1 . 1 Fox Chase Cancer Center, Philadelphia,
PA and 2 University of Alabama at Birmingham,
Birmingham, AL.
Monday
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