# CALORIES, FAT & SPONTANEOUS PROSTATE CANCER IN AGING RAT

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 1992 · $150,034

## Abstract

Prostate cancer (PC) is a major, understudied and poorly understood
geriatric problem.  Its occurrence depends on the presence of androgens and
has been associated with mutations in tumor suppressor genes.
Epidemiologic data suggest that diet and serum androstenedione levels may
influence the progression of latent forms of PC into more aggressive PC.
One prospective study linked high androstenedione levels with the later
development of PC.  As for diet, Japanese and Americans show similar
prevalences of latent PC but progression to clinical significance is rare
in Japan.  Yet, when Japanese migrate to the USA, an increased incidence of
malignant PC occurs suggesting the possibility of dietary influences.  A
study in Lobund-Wistar (LW) rats which provides a model of spontaneous and
metastatic PC supports a dietary role:  a modest calorie restriction (30%)
reduced PC incidence from 26% in controls to 6%.  All rats ate low fat diet
(5%) which is germane due to fat intake suggested as a risk factor.  This
result in LW rats agrees with a large literature showing that caloric
restriction of rodents retards cancer and aging.

Our broad goals are to elucidate molecular and cellular changes associated
with PC development and to evaluate dietary influences on these events.
Two hypotheses will be tested:  1) Plasma levels of androgens and/or
prolactin (another important regulator of prostatic growth) and the level
of prostate androgen receptor (AR) are risk factors for the development of
PC; and, 2) Influences of diet and aging on PC are linked to the frequency
of mutations in tumor suppressor genes and/or the AR gene.  To test these,
male LW rats will be fed a low fat (5%) diet ad lib until 12 mo old when
they will be assigned to one of four diet groups (n=70-80) and fed purified
diets designed to provide all rats with balanced intakes of protein,
vitamins and minerals but differing in calorie and fat intakes:  Group A)
Normal Calorie/Low Fat (N/L); rats fed ad lib via a 5% fat (corn oil) diet;
B) Normal Calorie/Medium Fat (N/M):  ad lib via a 15% fat diet; C) Low
Calorie/Medium Fat (L/M):  gradually restricted to 60% of ad lib intake via
a 15% fat, nutrient-enriched diet; D) Low Calorie/High Fat (L/H):
gradually restricted to 60% of ad lib via a 30% fat, nutrient-enriched
diet.  Rats will be killed at 12 mo of age (baseline) and at 6 mo intervals
thereafter over the life span.  The Specific Aims are to determine:  1) PC
prevalence (via histopathology); 2) androgen and prolactin levels (via RIA)
in serum; 3) AR levels (via flow cytometry) in normal prostate and in PC
cells; and, 4) mutation frequency of tumor suppressor genes (RB and p53)
and of the AR gene in PC cells (via Northern blot and polymerase chain
reaction).  The proposed studies will improve understanding of the
pathogenesis of PC and the extent to which it is sensitive to diet.  The
data should aid in the development of preventive and therapeutic
interventions to combat the alarming PC problem...

## Key facts

- **NIH application ID:** 3122425
- **Project number:** 1R01AG010536-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **SAM.gov UEI:** LCLSJAGTNZQ7
- **Principal Investigator:** Richard Weindruch
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $150,034
- **Award type:** 1
- **Project period:** 1992-05-01 → 1997-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122425

## Citation

> US National Institutes of Health, RePORTER application 3122425, CALORIES, FAT & SPONTANEOUS PROSTATE CANCER IN AGING RAT (1R01AG010536-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122425. Licensed CC0.

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