# POLYCYCLIC HYDROCARBON METABOLISM AND CARCINOGENESIS

> **NIH NIH R01** · DARTMOUTH COLLEGE · 1991 · $146,568

## Abstract

The overall research objective of this laboratory is to understand the
mechanism of regulation of cytochrome P450IA1, a monooxygenase that
functions in the activation of polycyclic hydrocarbons, such as benzo (a)
pyrene (BP).  We have postulated that a cytosolic 4S polycyclic
hydrocarbon-binding protein functions as a trans-activator of the P45OIA1
gene.  The specific aims of this proposal relate to this hypothesis.  The
specific aims are to: a) determine the amino acid sequence of the 4S
polycyclic hydrocarbon-binding protein, produce polyclonal antibodies to
this protein, and determine if phosphorylation and/or conjunction with
hsp90 can modify its activity; b) ascertain the nature of the 5'-upstream
regions of the P450IA1 gene to which the 4s protein binds, i.e., polycyclic
hydrocarbon responsive elements (PRE's), and establish by in vitro nuclear
transcriptional assays that the 4s protein is a trans-activator of this
gene; c) isolate the 4s protein gene from liver cDNA and genomic libraries
and characterize this gene, and d) determine the effects of transfection of
vectors that would transcribe antisense to the 4s gene and of introduction
of antibodies to the 4s protein on the induction of the P450IA1 gene in
response to BP treatment.  These studies should establish a central role
for the 4s polycyclic hydrocarbon-binding protein in the regulation of the
expression of the P450IA1 gene.

## Key facts

- **NIH application ID:** 3173598
- **Project number:** 2R01CA036106-09
- **Recipient organization:** DARTMOUTH COLLEGE
- **SAM.gov UEI:** EB8ASJBCFER9
- **Principal Investigator:** EDWARD BRESNICK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $146,568
- **Award type:** 2
- **Project period:** 1988-05-01 → 1994-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173598

## Citation

> US National Institutes of Health, RePORTER application 3173598, POLYCYCLIC HYDROCARBON METABOLISM AND CARCINOGENESIS (2R01CA036106-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173598. Licensed CC0.

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