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61742-02 Genistein Programming for Mammary Cancer Prevention
EDRI Federal Project Inventory:
61742-02 Genistein Programming for Mammary Cancer Prevention
Sponsor Organization: NIH/NCI
Project Title: 61742-02 GENISTEIN PROGRAMMING FOR MAMMARY CANCER PREVENTION
Project Focus: HUMAN HEALTH EFFECTS
Description: Breast cancer is one of the leading causes of human cancer.
Chemically-induced mammary cancer in rats provides amodel of
susceptibility for the study of carcinogenesis in human mammary
glands. Chemoprevention rather than cancertreatment is a preferred
means of health promotion. Our goal is to identify an efficacious
chemopreventive agent forhuman females inherently susceptible for
mammary cancer. In this interactive R0l we propose to investigate a
novelapproach, chemoprevention via critical period(s) of
development with a nutritional component of soy-based foods,i.e.,
genistein. Genistein is a phytoestrogen found in soy-based products,
the latter having been associated with a 2 to 5-fold lower incidence
of and death from breast cancer in women consuming soy products not
only as adults, but also pre-and postnatally. Estrogens given either
neonatally or just prior to carcinogen exposure have been shown to
preventmammary adenocarcinomas. Since genistein is a weak estrogen
agonist/antagonist, we hypothesize that it will exert achemopreventive
effect via imprinting mechanisms and/or developmental maturation of
the mammary when givenneonatally. Our experiments will l) determine if
biochemical imprinting during the neonatal period, or
prepubertalexposure to genistein will reduce the incidence of
dimethylbenz(a)anthracene-induced mammary adenocarcinomas, 2)
ifneonatal and prepubertal exposure to genistein will alter mammary
cell differentiation (using mammary whole mounts)and proliferation
(using PCNA/cyclin immunohistochemistry), and 3) if early genistein
exposure will alteractivation/detoxication mechanisms in the mammary.
The latter will be assessed by measuring the rate of formation
andpersistence of carcinogen-DNA adducts as a means of determining the
programming effect of genistein on initiationmechanisms of cancer.
References:
Category: MODELS
Subcategory: BASIC RESEARCH
Keywords for Experimental System/Species: IN VIVO
Keywords for Experimental Endpoints: CARCINOGENESIS, EMBRYO
Chemical Agents: PHYTOESTROGENS, GENISTEIN
Performing Institution: UNIVERSITY OF ALABAMA AT BIRMINGHAM
Contact: CONTRACT PERSON: ELAINE C. LEE; BUILDING 31; 11A21; NATIONAL CANCER
INSTITUTE, NIH,BETHESDA, MD 20892-2590; 301-496-5515;
LEEE@OD.NCI.NIH.GOV
