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EDRI Federal Project Inventory:
70478-01 Organochlorine Exposure and Breast Cancer Risk
- Sponsor Organization: NIH/NCI
- Project Title: 70478-01 ORGANOCHLORINE EXPOSURE AND BREAST CANCER RISK
- Project Focus: EXPOSURE ASSESSMENT
- Description: Recently, associations have been found between breast cancer risk and
organochlorine exposures as estimated fromblood and tissue levels of
residues. Therefore, organochlorine exposures may contribute to the
high breast cancer ratesin the U.S. Several organochlorines such as
DDT, PCB mixtures, and several PCB congeners have
considerableestrogenic activity. Endogenous estrogens are well
established breast cancer risk factors, and timing and duration
ofexposure is critical. This application addresses the hypothesis
that exposure to estrogenic organochlorines enhancesbreast cancer
development. Possible enhancing effects on breast carcinogenesis of
estrogenic organochlorine exposuremay be most profound when endogenous
estrogen production is low (before puberty or postmenopausal). To
test thishypothesis, the MNU mammary carcinogenesis model system in
the Sprague Dawley rat will be used to examine theinfluence on mammary
cancer development of well controlled exposure during specific time
periods to the estrogenicDDT isomer o,p-DDT and an estrogenic PCB
mixture Aroclor 1221. Thus, it will be determined whether
theseorganochlorines modify mammary cancer induction when administered
at the following times: (1) from 2 weeks after thecarcinogen
("promotion" stage); (2) subsequent to surgically-induced menopause
as surrogate for menopause in women("post-ovariectomy" stage); and (3)
from weaning (3 weeks of age) until carcinogen injection ("pre-
initiation" stage). Toachieve aim 3, it will be necessary to
compensate for possible organochlorine-induced shifts in the timing of
cellproliferation during puberty which is a critical element of the
single carcinogen dose mammary carcinogenesis model inthe rat.
Therefore, changes in the time of occurrence of cell proliferation in
the cellular target of carcinogens in thedeveloping mammary gland (the
terminal end-bud) will be determined with respect to organochlorine
exposure duringthe pre initiation and perinatal stages. The results of
these studies will demonstrate the mammary carcinogenesis-enhancing
potential of estrogenic organochlorines, and they will establish
differential effects of exposure at critical timesduring development
and aging in relation to environmental mammary carcinogenesis.
- References:
- Category: MODELS
- Subcategory: BASIC RESEARCH
- Keywords for Experimental System/Species: MAMMALIAN, LABORATORY STUDY
- Keywords for Experimental Endpoints: CARCINOGENESIS, PUBERTY, TISSUE RESIDUE, RISK FACTORS
- Chemical Agents: AROCHLOR 1221, PCB, o,p-DDT
- Performing Institution: NEW YORK UNIVERSITY
- Contact: CONTACT PERSON: ELAINE C. LEE; BUILDING 31; 11A21, NATIONAL CANCER
INSTITUTE, NIH,BETHESDA, MD 20892-2590; 301- 496-5515;
LEEE@OD.NCI.NIH.GOV
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