# SPECIFICITY OF DIOL EPOXIDE; CHROMATIN INTERACTIONS

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 1993 · $160,087

## Abstract

Environmental carcinogens of the polycyclic aromatic hydrocarbon class,
such as benzo(a)pyrene, are metabolized by cellular enzyme systems to
highly reactive bay-region diol epoxides which have been identified as
ultimate carcinogens.  These compounds modify macromolecules in cells,
thereby initiating the process of carcinogenesis.  Although the
interactions of benzo(a)pyrene diol epoxide (BPDE-I) with DNA have been
studied in vitro, little is known of how this relates to interactions which
take place in cellular nuclei, where the DNA is intimately associated with
a variety of chromosomal proteins.  Even less is known of the interactions
of BPDE-I with these proteins, nor of how such interactions may affect the
regulation of gene expression which involves interactions between DNA
control regions and trans-acting proteins.  In the present proposal,
several model systems will be studied in which a particular DNA-binding
protein and its target DNA can be prepared in large amounts utilizing
recombinant DNA technology.  The systems include the interaction of histone
proteins with DNA, the interaction of the human transcription factor Sp1
with the promoter of the aprt gene, the interaction of yeast transaction
factor SW15 with its target DNA in the HO gene, and the interaction of the
Xenopus transcription factor TFIIIA with the internal control region of the
5S RNA gene.  The latter three are all examples of zinc-finger
transcription factors, which appear to be of widespread importance.  The
following questions will be asked of these systems:  1) In nucleosomal
complexes of the histones with DNA, where are DNA binding sites for BPDE-I
located?  2) How does binding of the protein to its target DNA affect the
formation of covalent BPDE-I DNA adducts?  3) Does BPDE-I bind covalently
to the transcription factors?  If so, what are the target amino acid
residues and how is this binding affected by interaction with the target
DNA sequence?  4) What is the effect of BPDE-I-DNA adduct formation in a
target sequence upon the subsequent interaction with its cognate
transcription factor?

## Key facts

- **NIH application ID:** 3173180
- **Project number:** 5R01CA035581-10
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **SAM.gov UEI:** S3GMKS8ELA16
- **Principal Investigator:** Michael C MacLeod
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $160,087
- **Award type:** 5
- **Project period:** 1983-08-01 → 1995-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173180

## Citation

> US National Institutes of Health, RePORTER application 3173180, SPECIFICITY OF DIOL EPOXIDE; CHROMATIN INTERACTIONS (5R01CA035581-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173180. Licensed CC0.

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