# MECHANISM OF SKIN TUMOR PROMOTION BY CHRYSAROBIN

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 1991 · $143,584

## Abstract

Humans are continually exposed to a wide variety of chemicals,
some of which may act as initiators, promoters, cocarcinogens,
and/or complete carciongens.  Current evidence suggest that
tumor promotion plays an important role in the etiology of human
cancer.  Although the phorbol ester promoters have been widely
studied, much less is known about the mechanism of action of
anthrone tumor promoters.  While there are some similarities
between phorbol esters and the anthrones we have obtained
evidence that there are also some significant differences in their
effects on mouse skin.  In addition, indirect evidence which we
hav obtained suggests that oxidation of anthrones and generation
of free radicals is involved in their skin tumor promoting action.
The current proposal will continue to explore the mechanism of
skin tumor promotion by anthrones.  Specifically, we will explore
the role of anthrone oxidation and generation of free radicals in
skin tumor promotion by this class of compounds.  The specific
amis of the proposal are as follows:  (1) To further characterize
skin tumor promotion and progression by anthrone derivatives as
follows:  a) to examine the regression kinetics of papillomas
generated with various treatment protocols; b) to determine the
ability of anthrone derivatives to enhance progression of pre-
existing papillomas to carcinomas; and c) to further characterize
the phenomenon of delayed promotion leading to enchanced
promoting activity of anthrones; (2) To determine the ability of
anthrones to induce or activate polyamine interconversion
pathways in relation to epidermal toxicity and their skin tumor
promoting activity; (3) To determine the relationship(s) between
epidermal toxicity and anthrone mediated skin tumor promotion;
(4) To examine the nonenzymatic and enzymatic mechanisms for
oxidation of anthrones in mouse epidermis in relation to skin
tumor promotion.  Initial experiments indicate an excellent
correlation between the ability to undergo base catalyzed
oxidation and skin tumor promoting activity; (5) To determine the
nature of the reactive products of anthrone oxidation; (6) To
determine the ability of anthrones to modulate oxidant defense
systems in mouse epidermis; and (7) To determine the ability of
antioxidants to modulate skin tumor promotion by anthrones.  This
experimental approach will allow us to test the hypothesis that
anthrone skin tumor promoters work by a mechanism which
involves oxidation and subsequent generation of free radical
intermediates.

## Key facts

- **NIH application ID:** 3174808
- **Project number:** 5R01CA037111-09
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **SAM.gov UEI:** S3GMKS8ELA16
- **Principal Investigator:** John DiGiovanni
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $143,584
- **Award type:** 5
- **Project period:** 1983-08-01 → 1993-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174808

## Citation

> US National Institutes of Health, RePORTER application 3174808, MECHANISM OF SKIN TUMOR PROMOTION BY CHRYSAROBIN (5R01CA037111-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174808. Licensed CC0.

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