# ROLE OF DNA-BINDING IN SKIN TUMOR INITIATION

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 1990 · $144,125

## 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
covalent modification of DNA plays a central role in the
mechanism of tumor initiation by diverse classes of carcinogenic
agents including polycyclic aromatic hydrocarbons (PAH).
However, it remains to be determined which DNA-adducts are
most important; whether DNA-adducts are removed efficiently or
inefficiently thus introducing errors in the DNA; or whether DNA-
adducts must persist in the DNA for long periods of time for
tumor initiation.  The proposed research is designed to further
investigate the role of PAH DNA-adduct removal and persistence
in relation to skin tumor initiation in mice.  Mouse skin is a well
known target tissue for PAH and is a widely studied model system
for skin carcinogenesis.  The specific aims of the proposal are as
follows.  The quantitative relationship between the formation of
specific hydrocarbon DNA-adducts (especially dAdo adducts) and
skin tumor-initiation will be determined.  The extent and time
course of unscheduled DNA synthesis induced by a variety of
PAHs will be examined.  We will also examine the rates of
removal of specific DNA-adducts (especially dAdo adducts) in
relation to skin tumor-initiating potency.  Furthermore, we will
continue to explore the formation, removal, and persistence of
hydrocarbon DNA-adducts in epidermal subpopulations in
relation to the biphasic disappearance of DNA-adducts in mouse
epidermis.  We will further examine the role of DNA replication
at the time of tumor initiation by determining the quantitative
relationship between specific adduct formation and inhibition of
epidermal DNA synthesis and through the use of DNA synthesis
inhibitors.  Finally, to learn more about the biological,
biochemical and molecular effects of specific PAH DNA-adducts,
we will prepare site directed dAdo adducts from anti BPDE to be
incorporated into a bacterial vector.  This approach will allow us
to test the hypothesis that specific hydrocarbon DNA-adducts are
required early after application for skin tumor initiation.

## Key facts

- **NIH application ID:** 3174652
- **Project number:** 5R01CA036979-07
- **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:** $144,125
- **Award type:** 5
- **Project period:** 1984-03-01 → 1992-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174652

## Citation

> US National Institutes of Health, RePORTER application 3174652, ROLE OF DNA-BINDING IN SKIN TUMOR INITIATION (5R01CA036979-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174652. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*