# GENETICS OF SUSCEPTIBILITY TO SKIN TUMOR PROMOTION

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 1990 · $147,785

## Abstract

Humans are continually exposed to a wide variety of chemicals, some
of which may act as initiators, promoters, cocarcinogens and/or
complete carcinogens.  Current evidence suggests that the tumor
promotion stage of carcinogenesis plays an important role in the
etiology of human cancer.  The proposed research is designed to
further investigate the genetic factors controlling susceptibility
to skin tumor promotion by phorbol esters and other classes of
tumor promoters in inbred mouse strains.  Mouse skin is a well
known target tissue for many classes of promoters including phorbol
ester tumor promoters and is a widely studied model system for skin
carcinogenesis.  The specific aims are:  1) to further explore the
number of genes controlling susceptibility to skin tumor promotion
by phorbol esters in DBA/2 C3H/He,SSIn, C57BL/6, and other inbred
mouse strains as follows; a) to examine all available BXD RI
strains for sensitivity to TPA promotion; b) to examine the
sensitivity of B6C3F2, B6C3F1 x C57BL/6 (backcross), B6SSInF1,
B6SSInF2,and B6SSInF1 x C57BL/6 (backcross) mice to TPA promotion;
c) to examine all available BXH RI strains for sensitivity to TPA
promotion; and d) to continue to look for linkage in an attempt to
map TPA promotion sensitivity genes (see also #'s 3 and 4 below).
2) To determine the relative responsiveness of DBA/2, C57BL/6 mice
(and possibly other inbred strains) to different classes of skin
tumor promoting agents including indole alkaloids, polyacetates,
anthrones, and organic peroxides.  3) To determine whether
differences exist in the metabolism of phorbol esters between
inbred strains of mice; and 4) to determine whether differences
exist between inbred strains of mice with regard to the phorbol
ester receptor system (i.e., protein kinase C(PKC)), for:  a)
epidermal expression of isozymes of PKC; b) binding characteristics
of TPA, teleocidin, diacylglycerols and possible other derivatives
to epidermal PKC isozymes; c) translocation of epidermal PKC from
cytosol to membrane; and d) PKC isozyme down modulation.  This
approach will allow us to test the hypothesis that at least two
gene loci control susceptibility to skin tumor promotion by TPA in
DBA/2 mice and that at least one of these genes is related to
phorbol ester metabolism such as an esterase and/or the phorbol
ester receptor, PKC.

## Key facts

- **NIH application ID:** 3177260
- **Project number:** 5R01CA038871-06
- **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:** 1990
- **Award amount:** $147,785
- **Award type:** 5
- **Project period:** 1984-12-01 → 1991-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177260

## Citation

> US National Institutes of Health, RePORTER application 3177260, GENETICS OF SUSCEPTIBILITY TO SKIN TUMOR PROMOTION (5R01CA038871-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177260. Licensed CC0.

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