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NEW MODELS FOR COMPARATIVE STUDIES OF GONADAL TUMORS

Award Number: R01ES012066
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: HEALTH SERVICES
PERIOD OF PERFORMANCE START DATE: 12/16/1993
PERIOD OF PERFORMANCE END DATE: 07/31/2007

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NEW MODELS FOR COMPARATIVE STUDIES OF GONADAL TUMORS - DESCRIPTION (provided by applicant):Numerous findings have raised the level of national concern that chemicals found in the environment may have adverse effects on humans and wildlife. The Environmental Protection Agency's (EPA's) recent reassessment of dioxin toxicity concluded that body burdens of many individuals might exceed threshold levels that trigger developmental delays and hormonal changes. Additionally, this evaluation indicates that the dioxin-associated cancer risk is 10-fold higher than previous estimates. Environmental exposures have been implicated in contributing to gonadal tumors in eastern Maine softshell clams (M. arenaria); tumor prevalence as high as 40% has been observed in some feral populations. Tumor incidence has been correlated with the use of the herbicides 2,4 dichlorophenoxyacetic acid (2,4-D) and dioxin-contaminated 2,4,5-trichiorophenoxyactic acid (2,4,5-T). Epidemiological studies of women in the same geographical area document mortality rates from reproductive system cancers that are higher than the national average. These observations suggest that environmental exposures may contribute to the etiology of these cancers and to other reproductive effects. Understanding the molecular mechanisms by which tumors develop in the clam model may provide important information on the effect of chronic low-level environmental exposures and allow us to better extrapolate possible health risks to humans. Laboratory exposures established that bivalves accumulate dioxin, with the gonad serving as a reservoir. Dioxin exposure induced differential gene expression and both dioxin and herbicides had significant, negative impact on gametogenesis. The investigators have cloned a clam homologue to the vertebrate aryl hydrocarbon/dioxin receptor (AHR) that demonstrates structural similarity to human AHR. Continuation of these studies will focus on: 1) clam AHR characterization (e.g., ligand identification, protein-protein interactions, and biological activity); 2) further investigation of environmental toxicant impact on cell-cycle regulation pathways (e.g., stimulation of E3-mediated degradation of p53); and 3) short- and long-term laboratory exposures to herbicides and dioxin to evaluate effects on reproductive fitness.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2006 ( Subtotal = $251,205 )
2006	2006	UNIVERSITY OF MAINE, PORTLAND-GORHAM	96 FALMOUTH STREET	PORTLAND	ME	04103	CUMBERLAND	USA	Applied Toxicological Research and Testing	000	12	7/19/2006	NON-COMPETING CONTINUATION	$251,205
														Subtotal = $251,205

Issue Date FY: 2005 ( Subtotal = $257,250 )
2005	2005	UNIVERSITY OF MAINE, PORTLAND-GORHAM	96 FALMOUTH STREET	PORTLAND	ME	04103	CUMBERLAND	USA	Applied Toxicological Research and Testing	000	11	7/21/2005	NON-COMPETING CONTINUATION	$257,250
														Subtotal = $257,250

Issue Date FY: 2004 ( Subtotal = $257,250 )
2004	2004	UNIVERSITY OF MAINE, PORTLAND-GORHAM	96 FALMOUTH STREET	PORTLAND	ME	04103	CUMBERLAND	USA	Applied Toxicological Research and Testing	000	10	7/21/2004	NON-COMPETING CONTINUATION	$257,250
														Subtotal = $257,250

Issue Date FY: 2003 ( Subtotal = $257,250 )
2003	2003	UNIVERSITY OF MAINE, PORTLAND-GORHAM	96 FALMOUTH STREET	PORTLAND	ME	04103	CUMBERLAND	USA	Applied Toxicological Research and Testing	000	9	7/15/2003	NON-COMPETING CONTINUATION	$257,250
														Subtotal = $257,250

Issue Date FY: 2002 ( Subtotal = $282,250 )
2002	2002	UNIVERSITY OF MAINE, PORTLAND-GORHAM	96 FALMOUTH STREET	PORTLAND	ME	04103	CUMBERLAND	USA	Applied Toxicological Research and Testing	000	8	9/1/2002	OTHER REVISION	$282,250
														Subtotal = $282,250

Grand Total All Awards = $1,305,205

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NEW MODELS FOR COMPARATIVE STUDIES OF GONADAL TUMORS

Award Number: R01ES012066

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: HEALTH SERVICES

PERIOD OF PERFORMANCE START DATE: 12/16/1993

PERIOD OF PERFORMANCE END DATE: 07/31/2007

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