# STUDIES OF NON-B DNA STRUCTURE WITH CHEMICAL CARCINOGENS

> **NIH NIH R01** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 1987 · $188,378

## Abstract

The overall aim of this proposal is to test whether certain chemical
carcinogens preferentially react with putative regulatory regions in
chromatin which have "single-stranded" properties or exhibit a distinctly
high rate of "breathing."  (The term "single-stranded" will be used
operationally to describe such conformations in this proposal.)  Our long
term goal is to see whether such interactions of carcinogens with
"single-stranded" DNA structures could play a critical role in chemical
carcinogenesis.  The single-stranded DNA structures are generally known to
be more reactive to chemical carcinogens than double-stranded DNA.  We have
previously detected "single-stranded" conformation at specific sites in
chromatin employing a novel chemical probe called bromoacetaldehyde (BAA)
and have shown that such structures correlate with gene expression.  BAA is
extremely specific for unpaired DNA bases.  Also, BAA is a potential
chemical carcinogen since its less potent analogue, chloroacetaldehyde, is
carcinogenic.  For the purpose of studying where (that is, at which DNA
sequence) and how such DNA conformation occurs, we will first detect
"single-stranded" structures in specific protein:DNA complexes in vitro
using BAA as the tool.  Next, the features of the DNA sequences which are
prone to adopt non-B conformation ("single-stranded" structure) will be
studied using supercoiled plasmid DNA.  This approach is based on our
previous observation that DNA sequences detected by BAA in chromatin have
the potential of forming a non-B conformation containing "single-stranded"
properties in the purified supercoiled DNA form.  In addition to BAA, a
well known chemical carcinogen N-acetoxy-2-acetylaminofluorene
(N-acetoxy-AAF) will be tested to see if it can also recognize a similar
conformation.  This study will be extended to a cell culture system to map
the BAA and N-acetoxy-AAF binding sites in chromatin.  Lastly, the effect
on gene expression of chemical carcinogen binding to the regulatory region
of genes will be studied using a transient expression assay.

## Key facts

- **NIH application ID:** 3178985
- **Project number:** 5R01CA039681-03
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **SAM.gov UEI:** PHMKYKKJLQS1
- **Principal Investigator:** Terumi Kohwi-Shigematsu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $188,378
- **Award type:** 5
- **Project period:** 1985-04-01 → 1988-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178985

## Citation

> US National Institutes of Health, RePORTER application 3178985, STUDIES OF NON-B DNA STRUCTURE WITH CHEMICAL CARCINOGENS (5R01CA039681-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178985. Licensed CC0.

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