# POLYCYCLIC HYDROCARBON METABOLISM AND CARCINOGENESIS

> **NIH NIH R01** · DARTMOUTH COLLEGE · 1990 · $123,791

## Abstract

Our long-term objective is to understand the molecular basis for resistance
and susceptibility to polycyclic hydrocarbon-induced carcinogenesis.  We
have previously postulated that benzo(a)pyrene (BaP) and
3-methylcholanthrene (3MC) induce cytochrome P450c in the rat after
complexing with high affinity and in saturable manner to a 4S cytosolic
protein.  The latter would translocate into the nucleus, interact with a
specific region of the cytochrome P450c gene, and increase transcription of
this gene.  We have now purified the 4S binding protein and have formulated
the following specific aims for our investigations.  We will a) produce
monoclonal antibody to this purified protein, will characterize the
"receptor", localize this binding protein intracellularly, b) isolate the
gene for this 4S binding protein by screening a lambda gtll expression
library with either the antibody to this protein or with an oligonucleotide
probe, c) characterize the gene as to DNA sequence and cis-regulatory
elements, d) demonstrate that the 4S binding protein acts as a
transcriptional factor through the use of truncated cytochrome P450c gene
and in vitro transcriptional assay systems, e) isolate the 9S TCDD-binding
protein, prepare monoclonal antibody to it and differentiate this binding
protein from the 4S component, f) define the specific regions of
interaction of both the 4S and 9S binding proteins with the cytochrome
P450c gene, and g) convert a "receptor-negative" cell, such as early
passage RL-PR-C rat hepatocytes, to a "receptor-positive" one by
transfection and demonstrate the subsequent effects of this transfection on
the induction of cytochrome P450c.  We hope that through these specific
aims we will have a better understanding of the role of the binding
proteins in the induction of cytochrome P450c.

## Key facts

- **NIH application ID:** 3173602
- **Project number:** 5R01CA036106-08
- **Recipient organization:** DARTMOUTH COLLEGE
- **SAM.gov UEI:** EB8ASJBCFER9
- **Principal Investigator:** EDWARD BRESNICK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $123,791
- **Award type:** 5
- **Project period:** 1988-05-01 → 1991-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173602

## Citation

> US National Institutes of Health, RePORTER application 3173602, POLYCYCLIC HYDROCARBON METABOLISM AND CARCINOGENESIS (5R01CA036106-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173602. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*