# NON-B DAN STRUCTURE WITH CHEMICAL CARCINOGENS

> **NIH NIH R01** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 1991 · $261,026

## Abstract

The overall aim of the research proposed here is to understand how
non-B DNA structures rise at specific sites in chromosomal DNA
(which is hyperactive to certain chemical carcinogens) and to
understand the role of these non-B DNA structures in gene
expression.  Such DNA structure has been detected with a suspected
carcinogen, bromoacetalehyde (BAA), which is known to react
specifically with unpaired DNA bases.  Recently, related compound,
the known chemical carcinogen, chloroacetaldehyde (CAA), was also
found to react at the same sites in chromatin as were detected with
BAA.  When regulatory regions of genes in supercoiled plasmid DNA
are examined using BAA and CAA, multiple DNA sequences are found
which, under torsional stress, readily adopt non-B structure.  The
DNA sequences with this physical property are operationally defined
in his proposal as non-B sequences.  The CAA-reactive sites in
chromatin are usually found within or in close proximity to these
non-B sequences.  This proposal will test the hypothesis that non-
B sequences play an important role in active chromatin assembly nd
thus in regulation of gene expression.  To do this, the unusual
physical properties of non-B sequences found in the mouse
immunoglobulin  JH-C MuM intron will be analyzed.  The mechanism
by which certain non-B sequences argument level of gene expression
similarly to the polyoma enhancer when placed in an expression
system) will be investigated.  The functional properties of certain
non-B sequences and known enhancers will be compared.  The
possibilities for non-B sequences affecting nucleosome phasing, RNA
transcription initiation sites, and the interaction of host
cellular factors with their neighboring DNA sequences will be
studied.  The effect of DNA template topology on factor binding
potential will be determined.  A new minichromosome expression
system to study chromatin structure-function relationships will be
established.  The physical and functional analysis of non-B
sequences should facilitate understanding of the biological
significance of the target sites for certain chemical carcinogens
and thus the mechanism by which a carcinogen causes cancer.

## Key facts

- **NIH application ID:** 3178988
- **Project number:** 5R01CA039681-07
- **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:** 1991
- **Award amount:** $261,026
- **Award type:** 5
- **Project period:** 1985-04-01 → 1993-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178988

## Citation

> US National Institutes of Health, RePORTER application 3178988, NON-B DAN STRUCTURE WITH CHEMICAL CARCINOGENS (5R01CA039681-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178988. Licensed CC0.

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