# ROLE OF ARACHIDONATE METABOLITES IN TUMOR PROMOTION

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 1987 · $150,404

## Abstract

The goals of this investigation are the elucidation of the roles of
arachidonic acid (AA) metabolism in the tumor promotion stage of
mouse skin carcinogenesis.  Since inhibition of this metabolism
reduces papilloma incidence, it is proposed that at least some of
these AA metabolites have a direct or indirect role in the
processes needed for tumor development.  These functions will be
determined by addressing the following questions:  (1) Do specific
AA metabolites play a role in the normal and TPA induced growth
and differentiation processes of the epidermis?  The effect of the
principal prostaglandins (PGE/2, PGF/2 alpha and PGD/2) and the
predominant lipoxygenase products (5-, 12- and 5-HETE) on
proliferation and maturation parameters will be determined using
primary cultures of murine epidermis in defined media, in the
presence and absence of TPA and cyclooxygenase of lipoxygenase
inhibitors.  (2) Are the TPA-induced AA metabolites responsible
for the inflammation observed in SENCAR mice and is this
metabolism or inflammation important for the final carcinoma
incidence?  Inflammation will be quantitated by measuring
vascular permeability, edema and the cellular infiltrate
component in inbred SENCAR and C57B1/6 treated once or
repeatedly with tumor promoters, with and without
cyclooxygenase or lipoxgenase inhibitors.  It will be determined if
inhibitors of AA metabolism inhibit principally papilloma
formation or whether inhibition of conversion to carcinomas also
occurs.  (3) Does TPA alter immune responsiveness, are these
changes mediated in part by excessive arachidonate metabolism
and are the differences in response to TPA between C57B1/6 and
inbred SENCAR with regard to promotion due to differences in
immune response?  Selected parameters of the immune system
with emphasis on the skin will be measured  in nomal and TPA-
treated (once or multiply) inbred SENCAR and C57B1/6 mice:
Langerhans cells, T-helper and T-suppressor populations and
responses.

## Key facts

- **NIH application ID:** 3172123
- **Project number:** 2R01CA034443-04
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **SAM.gov UEI:** S3GMKS8ELA16
- **Principal Investigator:** SUSAN M FISCHER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $150,404
- **Award type:** 2
- **Project period:** 1984-07-01 → 1990-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172123

## Citation

> US National Institutes of Health, RePORTER application 3172123, ROLE OF ARACHIDONATE METABOLITES IN TUMOR PROMOTION (2R01CA034443-04). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3172123. Licensed CC0.

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