# SPECIFICITY OF DIOL EPOXIDE:  CHROMATIN INTERACTIONS

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 1988 · $161,502

## Abstract

Environmental carcinogens of the polynuclear 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.  In addition to modifying DNA, these electrophiles bind
covalently to proteins which are involved in chromatin structure.  In
particular, the ultimate carcinogen derived from B(a)P, B(a)P diol
epoxide-I (BPDE-I) binds specifically to histones H3 and H2A in intact
nuclei, intact cells and in purified chromatin.  We have very little
information concerning the effects of such protein lesions on the structure
and function of chromatin, effects which could be important in the process
of carcinogenesis.  We propose to extend our structural studies of this
binding reaction to the point where we can position the target sites in the
three-dimensional structure of the nucleosome.  We will determine
structural changes in nucleosomes induced by these adducts and we will use
an in vitro, eucaryotic transcription system to look for functional changes
which may accompany histone modification.  We will also begin to study the
effects of BPDE-I on the transcriptional control system which involves the
5S-RNA genes, the 5S transcripts and a positive transcriptional factor,
TFIIIA.

## Key facts

- **NIH application ID:** 3173177
- **Project number:** 5R01CA035581-06
- **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:** 1988
- **Award amount:** $161,502
- **Award type:** 5
- **Project period:** 1983-08-01 → 1990-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173177

## Citation

> US National Institutes of Health, RePORTER application 3173177, SPECIFICITY OF DIOL EPOXIDE:  CHROMATIN INTERACTIONS (5R01CA035581-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173177. Licensed CC0.

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