EDRI Federal Project Inventory:
58003-03s1 In Vitro Analysis of Estrogen Induced Tumorigenesis
- Sponsor Organization: NIH/NCI
- Project Title: 58003-03S1 IN VITRO ANALYSIS OF ESTROGEN INDUCED TUMORIGENESIS
- Project Focus: EXPOSURE ASSESSMENT
- Description: An estimated 40-6030f human cancers are associated with sex hormone
exposure. Examination of the importanceof estrogens as carcinogens or
cocarcinogens in the development of cancer requires evaluations of
estrogen effectsduring the various stages of estrogen-induced tumor
formation. One experimental model for examining the possiblerole(s)
of estrogens in tumor development is the Syrian hamster. Castrated
juvenile male golden Syrian hamsters andovariectomized female Syrian
hamsters will produce kidney tumors after prolonged exposure (9 to 12
months) to thesteroidal estrogen estradiol (E2) or to the nonsteroidal
estrogen diethylstilbestrol (DES). This unique in vivo model
ofestrogen carcinogenicity may provide important insights into the
molecular processes by which estrogens induce cancerdevelopment.
Recent research with this animal model in our laboratories has shown
that estrogens produce dysplasticfoci within three months of estrogen
treatment in hamsters and identified differences in the extent of
estrogen metabolismin primary kidney cell cultures and in kidney
tissue slices. The focus of our research is the elucidation of the
role(s) ofestrogens in biochemical events leading to tumor formation.
Our current working hypothesis is that continuous exposureof target
cells to estrogens results in hormonally-induced changes in cellular
biochemistry. These changes increase thevulnerability of the cells by
exposing critical regions of the DNA, by altering metabolism to
increase concentrations of potentially reactive compounds, and/or by
modifying levels of proteins important for growth and cell division.
Genotoxic and nongenotoxic insults at carcinogenic targets in the
hormonally-induced cell then result in phenotypicalterations in gene
expression. This collaborative, multidisciplinary proposal addresses
the hypothesis by developing invitro cell systems with varying
tumorigenic potential and analyzing the effects of various estrogens
(agonists,metabolites, antagonists) on parameters during stages of
tumorigenesis.
- References:
- Category: MODELS
- Subcategory: BASIC RESEARCH
- Keywords for Experimental System/Species: LABORATORY STUDY, IN VIVO, IN VITRO
- Keywords for Experimental Endpoints: MOLECULAR, GENE EXPRESSION, CARCINOGENESIS, SEX STEROIDS
- Chemical Agents: SEX HORMONES, ESTROGEN
- Performing Institution: OHIO STATE UNIVERSITY
- Contact: CONTACT PERSON:ELAINE C. LEE; BUILDING 31; 11A21, NATIONAL CANCER
INSTITUTE, NIH,BETHESDA, MD 20892-2590; 301 496-5515;
LEEE@0D.NCI.NIH.GOV
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