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EDRI Federal Project Inventory:
58088-04 Perinatal Hormonal Factors & Rat Prostate Carcinogenesis
- Sponsor Organization: NIH/NCI
- Project Title: 58088-04 PERINATAL HORMONAL FACTORS & RAT PROSTATE CARCINOGENESIS
- Project Focus: HUMAN HEALTH EFFECTS, EXPOSURE ASSESSMENT
- Description: Male human populations that are at high risk for prostate cancer often
have higher circulating testosterone levels thatpopulations that are
at lower risk for this disease. Circulating testosterone levels are
particularly high in pregnantwomen of high risk populations compared
with lower risk populations. Perinatal administration of considerable
doses ofdiethylstilbestrol (DES) to male mice causes carcinomas and
preneoplasia of the accessory sex glands, including theprostate.
These data suggest that prenatal exposure to DES and androgens
increases risk for prostate cancerdevelopment later in life. This
proposal seeks to test this hypothesis. We will expose male rats in
utero and/orneonatally to testosterone or DES at doses that are not
teratogenic or toxic, as to be determined in preliminary studies.
Subsequently, we will expose these rats to treatments that have been
shown to induce prostate cancer in rats that werenot exposed to
exogenous hormones perinatally. We will then compare the incidence,
multiplicity and latency ofprostate carcinomas in the perinatally
hormone exposed rats with these parameters in rats that were not
exposedprenatally. We will use three models of prostate cancer
induction that differ in their mechanism of action: (1)
chronictestosterone administration, (2) a single injection with N-
methyl-N-nitrosourea followed by chronic testosteroneadministration,
and (3) chronic administration of estradiol-17beta and testosterone.
In addition, we will determine the effects of perinatal androgen and
DES exposure on circulating testosterone and on androgen and estrogen
sensitivity ofthe male accessory sex glands, including the prostate.
- References:
- Category: MODELS
- Subcategory: BASIC RESEARCH
- Keywords for Experimental System/Species: LABORATORY STUDY, IN UTERO
- Keywords for Experimental Endpoints: MALE, CARCINOGENESIS, REPRODUCTIVE
- Chemical Agents: DIETHYLSTILBESTROL (DES), ANDROGENS, TESTOSTERONE, N-METHYL-
N- NITROSOUREA, ESTRADIOL-17BETA
- 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@0D.NCI.NIH.GOV
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