# IN VIVO IMMUNOTOXICOLOGY OF TUMOR-PROMOTING AGENTS

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 1987 · $189,008

## Abstract

Studies in this laboratory have shown qualitative and quantitative
alterations in several different immunofunctional cell types
following topical application of phorbol diesters at tumor-
promoting doses.  Evidence for a role of such alterations in the
promotion process was thereby provided, and indicated in which
stageof the latter individual changes were most important.  We
havedemonstrated in this way that overall promoter-induced
spleen cell proliferation was predominantly a consequence of
inflammation, and may be relevant only in the later stages of
promotion.  On the other hand promoter-induced proliferation of
GMCFU progenitor cells was apparently not, and was inhibited
by inhibitors of promotion with inhibitory activity toward specific
pathways of arachidonic acid metabolism.  These findings strongly
indicated a role for GM-CFU cells in promotion, but also a need
todetermine underlying mechanisms.  These include whether the
increase proliferation was due to i) systemic promoter effects of
viarelease of soluble Interleukin 3 or Colony-Stimulating Factor
fromskin cells and ii) due to increased traffic from the marrow
rather than proliferation in situ.

Afurther finding in this laboratory was a reduction in number of
Thy1+epidermal cells following topical promoter application,
together with a morphological change in these and Ia+ Langerhans
cellsTo further investigate the responses of these cells to
promoting agents, the following parameters will be measured:

i)  Cell densities in epidermal sheets.
ii)  Cellfunctions following purification by sorting:  Interleukin
1production and ability to induce contact hypersensitivity CH)
for Langerhans cells, and ability to down-regulate CH forThy-1+
cells.

The role of observed alterations in the above parameters in the
tumor promotion process will be assessed using:

i)  Agents with different relative tumor-promoting and
inflammatory activities.
ii)  Agents which inhibit promotion and inflammation to different
degrees.
iii)  Brief and prolonged exposures to the above agents and
modifiers, comparing resultant inflammatory and
immunomodulatory responses.  Inflammatory/promoting agents
will be used with inflammatory activity which persists to
different degrees.  Additional studies in initiated animals will also
enable alterations in immune cells to be temporally related to
tumor appearance.

## Key facts

- **NIH application ID:** 3172132
- **Project number:** 2R01CA034446-04
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **SAM.gov UEI:** DZ4YCZ3QSPR5
- **Principal Investigator:** Charles Stuart Baxter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $189,008
- **Award type:** 2
- **Project period:** 1984-07-15 → 1990-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172132

## Citation

> US National Institutes of Health, RePORTER application 3172132, IN VIVO IMMUNOTOXICOLOGY OF TUMOR-PROMOTING AGENTS (2R01CA034446-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172132. Licensed CC0.

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