Program - Society of Toxicology

44 th Annual Meeting
and ToxExpo
Program Description
TUESDAY
3:20 PM Funding Alternatives to NIH: Being Creative,
Jean F. Regal, University of Minnesota Medical
School, Duluth, MN.
Tuesday Afternoon, March 8
1:30 PM to 4:30 PM
Room RO1
SYMPOSIUM SESSION: THE AHR IN CELL GROWTH AND DEATH
Chairperson(s): David Sherr, Boston University School of Public Health,
Boston, MA and Prakash Nagarkatti, Virginia Commonwealth University,
Richmond, VA.
Endorsed by:
Immunotoxicology SS
Since its first description as a dioxin-binding protein in the 1980s, the aryl
hydrocarbon receptor (AhR) has been studied primarily for its control of
biologic responses to environmental agonists. However, in the last few years it
has become apparent that the AhR, which clearly did not evolve to recognize
environmental pollutants, likely plays an important physiologic function.
Indeed, the ability of the AhR to directly regulate important cellular genes and
factors such as Bax, the estrogen receptor, Rb, and NF-kB hints at a critical role
for the AhR in cell growth and death. The presence of constitutively active AhR
in cells that exhibit aberrant growth and apoptosis regulation, i.e. neoplastic
cells, further supports this hypothesis. In this symposium we will present several
examples of AhR-mediated control of cell growth and death and will begin to
detail the molecular mechanisms through which this control is manifest. In
some studies presented herein, AhR function is revealed with exogenous
agonists such as TCDD or PAH. In other cases, constitutive AhR function is
demonstrated by modulation of AhR expression and activity in the absence of
exogenous ligands. In all cases, the roles that the AhR may play in normal
cellular physiology and the consequences of disrupting these functions with
environmental agonists are discussed.
#990 1:30 THE AHR IN CELL GROWTH AND DEATH. D. H.
Sherr 1 and P. Nagarkatti 2 . 1 Environmental Health,
Boston University School of Public Health, Boston, MA
and 2 Department of Pharmacology and Toxicology,
Virginia Commonwealth Unviersity, Richmond, VA.
#991 1:40 LIGATION OF AHR LEADS TO UP-
REGULATION OF APOPTOTIC GENES
THROUGH DRE-DEPENDENT AND -
INDEPENDENT PATHWAYS INVOLVING NF-KB
AND CONSEQUENT INDUCTION OF
APOPTOSIS IN THYMOCYTES. P. S. Nagarkatti.
Pharmacology and Toxicology, Medical College of
Virginia Campus, Virginia Commonwealth University,
Richmond, VA.
#992 2:10 AHR CONTROL OF B LYMPHOCYTE DEATH
AND GROWTH. S. H. David, H. Ryu, J. K. Emberley,
L. L. Allan and J. J. Schlezinger. Environmental Health,
Boston University School of Public Health, Boston,
MA.
#993 2:40 REGULATION OF MAMMARY TUMOR
GROWTH THROUGH THE ARYL
HYDROCARBON RECEPTOR. S. H. Safe.
Veterinary Physiology, Texas A & M University,
College Station, TX.
#994 3:10 CURRENT INSIGHTS INTO AHR-MEDIATED
LIVER CELL CYCLE CONTROL. C. J. Elferink.
Pharmacology and Toxicology, University of Texas
Medical Branch, Galveston, TX. Sponsor: D. Sherr.
#995 3:40 AHR CONTROL OF APOPTOSIS INDUCED BY
AGENTS CAUSING LYSOSOMAL DAMAGE. J. J.
Reiners. Institute of Environmental Health Sciences,
Wayne State University, Detroit, MI. Sponsor: D.
Sherr.
Tuesday Afternoon, March 8
1:30 PM to 4:30 PM
Room RO4
SYMPOSIUM SESSION: ORGANOPHOSPATES & CARBMATES:
CHOLINERGIC VS. NONCHOLINERGIC MECHANISMS
Chairperson(s): Ramesh Gupta, Murray State University, Hopkinsville, KY
and Carey N. Pope, Oklahoma State University, Stillwater, OK.
Endorsed by:
Comparative and Veterinary SS
Neurotoxicology SS*
Risk Assessment SS
Student Advisory Committee
Organophosphates (OPs) and carbamates (CMs) are commonly used as pesticides
in agriculture, industry, and around the home/garden. Some OPs have also
been used in chemical warfare and terrorism, while some CMs have been used
to treat diseases such as myasthenia gravis and dementia. Interestingly, the CM
pyridostigmine is used prophylactically to protect soldiers from possible OP
nerve agent exposure. Many compounds of both classes are extremely toxic and
lack selectivity, thus their inadvertent/accidental use continues to pose a threat
to human and animal health, aquatic systems and wildlife. While these
compounds have a wide variety of toxic effects, neurotoxicity elicited by inhibition
of acetylcholinesterase (AChE) is generally of primary concern. In recent
years, a variety of novel mechanisms for OPs and CMs have been proposed
which may modulate cholinergic neurotoxicity or lead to non-cholinergic
effects. Molecular studies of AChE and its interaction with inhibitors has
allowed a more thorough characterization of the structure, function, and regulation
of this enzyme. In vitro studies indicate that NGF-differentiated SY5Y cells
may distinguish between OPs that produce OPIDN and those that do not, and
may therefore be a suitable mechanistic model for exploring the effects of
different classes of OPs. Evidence suggests that while cholinergic mechanisms
play a critical role in the initial stage of cholinergic toxicity, neuronal
damage/death may occur through non-cholinergic mechanisms including oxidative
stress. The Food Quality Protection Act of 1996 requires EPA to consider
the cumulative risk to pesticides with a common mechanism of action. In the
case of OPs and CMs, this common mechanism is initiated by inhibition of
AChE (via phosphorylation or carbamylation, respectively). However,
noncholinergic mechanisms are not currently considered in risk assessment.
This symposium will review the latest developments in understanding of molecular
mechanisms (cholinergic and non-cholinergic) for these toxicants, as well
as discuss current strategies of cumulative risk assessment for pesticides acting
through a common mechanism.
#996 1:30 ORGANOPHOSPHATES & CARBAMATES:
CHOLINERGIC & NONCHOLINERGIC
MECHANISMS. R. C. Gupta. Toxicology, Murray
State University, Hopkinsville, KY.
#997 1:40 CONTEMPORARY PROTEOMICS IN
ACETYLCHOLINESTERASE AND RELATED α,
β HYDROLASE-FOLD PROTEINS AS TARGETS
OF TOXICOLOGICAL MANIFESTATIONS AND
GENETIC DISORDERS. P. Taylor, Z. Radic, L.
Jennings and S. Camp. Pharmacology, University of
California, San Diego, La Jolla, CA. Sponsor: R.
Gupta.
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SOT’s 44 th Annual Meeting