# EICOSANOIDS AND MAMMARY CANCER

> **NIH NIH R01** · ROSWELL PARK CANCER INSTITUTE · 1989 · $123,038

## Abstract

The objective is to determine the effect of the lipoxygenase and
cyclooxygenase products of arachidonic acid metabolism (eicosanoids) on the
growth of normal and transformed mammary cells.  It is our hypothesis that
certain lipoxygenase products, formed in increased amounts in the presence
of cyclooxygenase inhibitors by diversion of arachidonic acid into the
lipoxygenase pathways, or by actual stimulation of a lipoxygenase, may plan
a beneficial role in the reduction of tumorigenesis and the inhibition of
growth of transformed mammary cells.  The following studies will address
this question.  1. To determine the role of lipoxygenase and cyclooxygenase
products in the growth of normal and transformed mammary cells in vivo.
Specifically, the effects of cyclooxygenase inhibitors iwll be compared
with those of dual cyclooxygenase plus lipoxygenase inhibitors on
DMBA-induced mammary carcinogenesis and these effects will be correlated
with changes in the products of the 5-, 12- and 15-lipoxygenases, as well
as cyclooxygenase, in mammary gland, mammary tumor and blood.  2. To
determine if changes in arachidonate content of mammary gland phospholipids
can modulate the efficacy of the cyclooxygenase inhibitor indomethacin on
DMBA-induced mammary carcinogenesis.  3. To determine if the inhibitory
effect of diets containing high levels of fish oil on DMBA-induced mammary
carcinogenesis is correlated with changes in the fatty acid content of
mammary gland membrane phospholipids and of levels of mammary gland and
mammary tumor arachidonic acid metabolites.  Aim 4. To determine the role
of lipoxygenase and cyclooxygenase products in the growth of normal and
transformed mammary cells in vitro.  Specifically, production of
arachidonic acid metabolites will be compared in both normal rat mammary
epithelial cells and DMBA-induced rat mammary tumor cells in primary
culture under basal, hormone- and Ca++ ionophore-stimulated conditions.  In
addition, the effects of cyclooxygenase and lipoxygenase inhibitors will be
compared in terms of their ability to alter growth of both normal and
transformed mammary cells and the effects will be correlated with changes
in levels of arachidonic acid metabolites.  Studies will also be done to
determine if changes in the fatty acid composition of membrane
phospholipids alter the efficacy of the cyclooxygenase and lipoxygenase
inhibitors, or of eicosanoid production under basal or stimulated
conditions.

## Key facts

- **NIH application ID:** 3173243
- **Project number:** 5R01CA035641-06
- **Recipient organization:** ROSWELL PARK CANCER INSTITUTE
- **Principal Investigator:** MARGOT M IP
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $123,038
- **Award type:** 5
- **Project period:** 1983-08-01 → 1991-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173243

## Citation

> US National Institutes of Health, RePORTER application 3173243, EICOSANOIDS AND MAMMARY CANCER (5R01CA035641-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173243. Licensed CC0.

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