The long term objective of this program is to characterize the dog as a model for monitoring the impact of PCB and other environmental contaminants on the immune system. A panel of tests have been developed based on laboratory exposure of dogs to levels of PCB (Aroclor 1248) commonly found around superfund sites. Many of the immune and non-immune aberrations described appear unusual. For this reason, we propose to: (1) evaluate the sensitivity of the panel by exposing dogs to varying levels of dietary PCB (100 microg 2 mg/kg); (2) evaluate the contribution of PCB-induced hypothyroidism to immunologic changes, delayed wound healing, weight loss and behavioral changes by comparing PCB fed, control and thyroidectomized dogs before and after oral supplementation with triiodothyronine (T3). To evaluate the efficacy of T3 therapy on immune system restoration and evaluate the metabolism of thyroxine (T4) by measuring T4 half-life in control and PCB fed dogs; (3) to probe the fundamental mechanisms responsible for PCB-induced hypogammaglobulinemia A and M. Studies will focus on the appropriateness of B-cell Ig class switching in PCB and normal dogs, circulating half-life of canine IgA and IgM in PCB fed and control dogs and the use of in vitro techniques to study B-cell de-novo antibody synthesis and its relationship to cell proliferation, cytokine synthesis, response to cytokines and response to alternative signal transduction. Increased cellular proliferation was documented in PCB fed dogs by blastogenesis testing, histology and measuring p34cdc-2 kinase. The latter was elevated in all PCB fed dogs and is a major regulator of cell cycle induction and progression. We will evaluate levels of p34cdc-2 kinase in lymphoid tissues of dogs fed PCB to determine if activation is present, dose dependent and associated with hyper- and hypoproliferation states. (5) Dogs will be evaluated in households selected on the basis of known exposure risk (Akwesasne Nation Community) using the field test panel. Of the seven tests conducted in dogs, five will be quantitated in humans sharing the household (by N.Y.S.D.O.H.). We will compare results of our panel in dogs with other household occupants and attempt to correlate physiological changes with. PCB levels and exposure risk. Two tests will be conducted in wild caught shrews from the same geographic site. Through these studies we hope to have a greater understanding of the basic mechanisms involved in PCB toxicity. The dog model will provide immunologic and endocrine targets for PCB activity. We shall determine the lowest concentration of PCB which can pose a toxic risk to dogs (and humans) and we shall validate or panel of biomarkers in dogs by cross-comparison to humans and wildlife which share the environment with dogs.

Project Start
1998-04-01
Project End
1999-03-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
7
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Cornell University
Department
Type
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Smith, Donald; Strupp, Barbara J (2013) The scientific basis for chelation: animal studies and lead chelation. J Med Toxicol 9:326-38
Beaudin, Stephane A; Stangle, Diane E; Smith, Donald R et al. (2007) Succimer chelation normalizes reactivity to reward omission and errors in lead-exposed rats. Neurotoxicol Teratol 29:188-202
Stangle, Diane E; Smith, Donald R; Beaudin, Stephane A et al. (2007) Succimer chelation improves learning, attention, and arousal regulation in lead-exposed rats but produces lasting cognitive impairment in the absence of lead exposure. Environ Health Perspect 115:201-9
Quimby, Fred W; Casey, Ann C; Arquette, Mary Fadden (2005) From dogs to frogs: how pets, laboratory animals, and wildlife aided in elucidating harmful effects arising from a hazardous dumpsite. ILAR J 46:364-9
Chen, Suping; Golemboski, Karen; Piepenbrink, Michael et al. (2004) Developmental immunotoxicity of lead in the rat: influence of maternal diet. J Toxicol Environ Health A 67:495-511
Stangle, Diane E; Strawderman, Myla S; Smith, Donald et al. (2004) Reductions in blood lead overestimate reductions in brain lead following repeated succimer regimens in a rodent model of childhood lead exposure. Environ Health Perspect 112:302-8
Driscoll, Lori L; Carroll, Jenna C; Moon, Jisook et al. (2004) Impaired sustained attention and error-induced stereotypy in the aged Ts65Dn mouse: a mouse model of Down syndrome and Alzheimer's disease. Behav Neurosci 118:1196-205
Lee, Ji-Eun; Dietert, Rodney R (2003) Developmental immunotoxicity of lead: impact on thymic function. Birth Defects Res A Clin Mol Teratol 67:861-7
Savage, Wesley K; Quimby, Fred W; DeCaprio, Anthony P (2002) Lethal and sublethal effects of polychlorinated biphenyls on Rana sylvatica tadpoles. Environ Toxicol Chem 21:168-74
Tang, Jixin; Liste, Hans-Holger; Alexander, Martin (2002) Chemical assays of availability to earthworms of polycyclic aromatic hydrocarbons in soil. Chemosphere 48:35-42

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